• 1
    Boettner, E. A. and J. R. Wolter (1962) Transmission of the ocular media. Investig. Ophthalmol. 1, 776783.
  • 2
    Lerman, S. (1987) Effects of sunlight on the eye. In Photomedicine (Edited by E.Ben Hur and I.Rosenthal), pp. 79121. CRC Press, Boca Raton .
  • 3
    Sliney, D. H. (2002) How light reaches the eye and its components. Int. J. Toxicol. 21, 501509.
  • 4
    Dillon, J., L. Zheng, J. C. Merriam and E. R. Gaillard (2004) Transmission of light to the aging human retina: possible implications for age related macular degeneration. Exp. Eye Res. 79, 753759.
  • 5
    Sliney, D. H. (2001) Photoprotection of the eye—UV radiation and sunglasses. J. Photochem. Photobiol. B-Biol. 64, 166175.
  • 6
    Naidoff, M. A. and D. H. Sliney (1974) Retinal injury from a welding arc. Am. J. Ophthalmol. 77, 663668.
  • 7
    Romanchuk, K. G., V. Pollak and R. J. Schneider (1978) Retinal burn from a welding arc. Can. J. Ophthalmol. 13, 120122.
  • 8
    Schatz, P., U. Eriksson, V. Ponjavic and S. Andreasson (2004) Multifocal electroretinography and optical coherence tomography in two patients with solar retinopathy. Acta Ophthalmol. Scand, 82, 47680.
  • 9
    Young, R. W. (1988) Solar radiation and age-related macular degeneration. Surv. Ophthalmol. 32, 252269.
  • 10
    Ham, W. T., H. A. Mueller, J. J. J. Ruffolo and D. I. Guerry (1980) Solar retinopathy as a function of wavelength: its significance for protective eyewear. In The Effects of Constant Light on Visual Processes (Edited by T. P.Williams and B. N.Baker), pp. 319346. Plenum Press, New York .
  • 11
    Tso, M. O. and F. G. La Piana (1974) The human fovea after sungazing. Trans. Sect. Ophthalmol. Am. Acad. Ophthalmol. Otolaryngol. 79, 788795.
  • 12
    Green, W. R. and D. M. Robertson (1991) Pathologic findings of photic retinopathy in the human eye. Am. J. Ophthalmol. 112, 520527.
  • 13
    Hope-Ross, M. W., G. J. Mahon, T. A. Gardiner and D. B. Archer (1993) Ultrastructural findings in solar retinopathy. Eye 7, 2933.
  • 14
    Friedman, E. and T. Kuwabara (1968) The retinal pigment epithelium. IV. The damaging effects of radiant energy. Arch. Ophthalmol. 80, 265279.
  • 15
    Ham, W. Jr, J. Ruffolo Jr, H. Mueller, A. Clarke and M. Moon (1978) Histologic analysis of photochemical lesions produced in rhesus retina by short-wavelength light. Investig. Ophthalmol. Vis. Sci. 17, 10291035.
  • 16
    Parver, L. M., C. R. Auker and B. S. Fine (1983) Observations on monkey eyes exposed to light from an operating microscope. Ophthalmology 90, 964972.
  • 17
    Kirkness, C. M. (1986) Do ophthalmic instruments pose a hazard of light-induced damage to the eye? In Hazards of Light; Myths & Realities; Eye and Skin, 1st edition (Edited by J.Cronly-Dillon, E. S.Rosen and J.Marshall), pp. 179186. Pergamon Press, Oxford .
  • 18
    Sliney, D. H. (1997) Optical radiation safety of medical light sources. Phys. Med. Biol. 42, 981996.
  • 19
    Michels, M. and P. Sternberg (1990) Operating microscope induced retinal phototoxicity—pathophysiology, clinical manifestations and prevention. Surv. Ophthalmol. 34, 237252.
  • 20
    McDonald, H. R. and A. R. Irvine (1983) Light-Induced maculopathy from the operating microscope in extracapsular cataract-extraction and intraocular-lens implantation. Ophthalmology 90, 945951.
  • 21
    McDonald, H. R. and M. J. Harris (1988) Operating microscope- induced retinal phototoxicity during pars plana vitrectomy. Arch, Ophthalmol. 106, 521523.
  • 22
    Poliner, L. S. and P. E. Tornambe (1992) Retinal pigment epitheliopathy after macular hole surgery. Ophthalmology 99, 16711677.
  • 23
    Michels, M., H. Lewis, G. W. Abrams, D. P. Han, W. F. Mieler and J. Neitz (1992) Macular phototoxicity caused by fiberoptic endoillumination during pars-plana vitrectomy. Am. J. Ophthalmol. 114, 287296.
  • 24
    Sliney, D. H. (1983) Eye protective techniques for bright light. Ophthalmology 90, 937944.
  • 25
    Stringham, J. M., K. Fuld and A. J. Wenzel (2003) Action spectrum for photophobia. J. Opt. Soc. Am. A-Opt. Image Sci. Vis. 20, 18521858.
  • 26
    Marlor, R. L., B. R. Blais, F. R. Preston and D. G. Boyden (1973) Foveomacular retinitis, an important problem in military medicine: epidemiology. Investig. Ophthalmol. 12, 516.
  • 27
    Tomany, S. C., K. J. Cruickshanks, R. Klein, B. E. K. Klein and M. D. Knudtson (2004) Sunlight and the 10-year incidence of age-related maculopathy—the Beaver Dam Eye Study. Arch. Ophthalmol, 122, 750757.
  • 28
    Taylor, H. R., S. West, B. Munoz, F. S. Rosenthal, S. B. Bressler and N. M. Bressler (1992) The long-term effects of visible-light on the eye. Arch. Ophthalmol. 110, 99104.
  • 29
    Klein, R., T. Peto, A. Bird and M. R. Vannewkirk (2004) The epidemiology of age-related macular degeneration. Am. J. Ophthalmol. 137, 486495.
  • 30
    van Leeuwen, R., C. C. W. Klaver, J. R. Vingerling, A. Hofman and P. de Jong (2003) Epidemiology of age-related maculopathy: a review. Eur. J. Epidemiol. 18, 845854.
  • 31
    de Jong, P. and J. Lubsen (2004) The standard gamble between cataract extraction and AMD. Graefes Arch. Clin. Exp. Ophthalmol. 242, 103105.
  • 32
    Khwarg, S. G., F. A. Linstone, S. A. Daniels, S. J. Isenberg, T. A. Hanscom, M. Geoghegan and B. R. Straatsma (1987) Incidence, risk factors, and morphology in operating microscope light retinopathy. Am. J. Ophthalmol. 103, 255263.
  • 33
    Mainster, M. A. and J. R. Sparrow (2003) How much blue light should an IOL transmit? Br. J. Ophthalmol. 87, 15231528.
  • 34
    Peyman, G. A., R. Zak and H. Sloane (1983) Ultraviolet-absorbing pseudophakos: an efficacy study. J. Am. Intraocul. Implant. Soc. 9, 161170.
  • 35
    Dowling, J. E. and R. L. Sidman (1962) Inherited retinal dystrophy in the rat. J. Cell Biol. 14, 73109.
  • 36
    Heckenlively, J. R., J. A. Rodriguez and S. P. Daiger (1991) Autosomal dominant sectoral retinitis-pigmentosa—2 families with transversion mutation in codon 23 of rhodopsin. Arch. Ophthalmol. 109, 8491.
  • 37
    Noorwez, S. M., R. Malhotra, J. H. McDowell, K. A. Smith, M. P. Krebs and S. Kaushal (2004) Retinoids assist the cellular folding of the autosomal dominant retinitis pigmentosa opsin mutant P23H. J. Biol. Chem. 279, 1627816284.
  • 38
    Naash, M. L., N. S. Peachey, Z. Y. Li, C. C. Gryczan, Y. Goto, J. Blanks, A. H. Milam and H. Ripps (1996) Light-induced acceleration of photoreceptor degeneration in transgenic mice expressing mutant rhodopsin. Investig. Ophthalmol. Vis. Sci. 37, 775782.
  • 39
    Organisciak, D. T., R. A. Darrow, L. Barsalou, R. K. Kutty and B. Wiggert (2003) Susceptibility to retinal light damage in transgenic rats with rhodopsin mutations. Investig. Ophthalmol. Vis. Sci. 44, 486492.
  • 40
    Vaughan, D. K., S. F. Coulibaly, R. M. Darrow and D. T. Organisciak (2003) A morphometric study of light-induced damage in transgenic rat models of retinitis pigmentosa. Investig. Ophthalmol. Vis. Sci. 44, 848855.
  • 41
    LaVail, M. M., G. M. Gorrin, D. Yasumura and M. T. Matthes (1999) Increased susceptibility to constant light in nr and pcd mice with inherited retinal degenerations. Investig. Ophthalmol. Vis. Sci. 40, 10201024.
  • 42
    Wang, M., T. T. Lam, M. O. M. Tso and M. I. Naash (1997) Expression of a mutant opsin gene increases the susceptibility of the retina to light damage. Vis. Neurosci. 14, 5562.
  • 43
    Tso, M. O. M. and B. J. Woodford (1983) Effect of photic injury on the retinal tissues. Ophthalmology 90, 952963.
  • 44
    Lawwill, T. (1982) Three major pathologic processes caused by light in the primate retina: a search for mechanisms. Trans. Am. Ophthalmol. Soc. 80, 517579.
  • 45
    Irvine, A. R., I. Wood and B. W. Morris (1984) Retinal damage from the illumination of the operating microscope—an experimental study in pseudophakic monkeys. Arch. Ophthalmol. 102, 13581365.
  • 46
    Reme, C. E., F. Hafezi, A. Marti, K. Munz and J. J. Reinboth (1998) Light damage to retina and retinal pigment epithelium. In The Retinal Pigment Epithelium (Edited by M.Marmor and T.Wolfensberger), pp. 563586. Oxford University Press, Oxford .
  • 47
    Reme, C. E., C. Grimm, F. Hafezi, A. Marti and A. Wenzel (1998) Apoptotic cell death in retinal degenerations. Prog. Retin. Eye Res. 17, 443464.
  • 48
    Organisciak, D. T. and B. S. Winkler (1994) Retinal light damage: practical and theoretical considerations. Prog. Retin. Eye Res. 13, 129.
  • 49
    Lanum, J. (1978) The damaging effects of light on the retina. Empirical findings, theoretical and practical implications. Surv. Ophthalmol. 22, 221249.
  • 50
    Hafezi, F., A. Marti, K. Munz and C. E. Reme (1997) Light-induced apoptosis: differential timing in the retina and pigment epithelium. Exp. Eye Res. 64, 963970.
  • 51
    Yu, D. Y. and S. J. Cringle (2001) Oxygen distribution and consumption within the retina in vascularised and avascular retinas and in animal models of retinal disease. Prog. Retin. Eye Res. 20, 175208.
  • 52
    Wangsa-Wirawan, N. D. and R. A. Linsenmeier (2003) Retinal oxygen—fundamental and clinical aspects. Arch. Ophthalmol. 121, 547557.
  • 53
    Bok, D. (1993) The retinal-pigment epithelium—a versatile partner in vision. J. Cell Sci. 17, 189195.
  • 54
    Wenzel, A., C. Grimm, M. Samardzija and C. E. Reme (2005) Molecular mechanisms of light-induced photoreceptor apoptosis and neuroprotection for retinal degeneration. Prog. Retin. Eye Res. 24, 275306.
  • 55
    Williams, T. P. and W. L. Howell (1983) Action spectrum of retinal light-damage in albino rats. Investig. Ophthalmol. Vis. Sci. 24, 285287.
  • 56
    Noell, W. K., V. S. Walker, B. S. Kang and S. Berman (1966) Retinal damage by light in rats. Investig. Ophthalmol. 5, 450473.
  • 57
    Li, F., W. Cao and R. E. Anderson (2003) Alleviation of constant-light-induced photoreceptor degeneration by adaptation of adult albino rat to bright cyclic light. Investig. Ophthalmol. Vis. Sci. 44, 49684975.
  • 58
    Ohira, A., M. Tanito, S. Kaidzu and T. Kondo (2003) Glutathione peroxidase induced in rat retinas to counteract photic injury. Investig. Ophthalmol. Vis. Sci. 44, 12301236.
  • 59
    Penn, J. S., M. I. Naash and R. E. Anderson (1987) Effect of light history on retinal antioxidants and light damage susceptibility in the rat. Exp. Eye Res. 44, 779788.
  • 60
    Wiegand, R. D., C. D. Joel, L. M. Rapp, J. C. Nielsen, M. B. Maude and R. E. Anderson (1986) Polyunsaturated fatty acids and vitamin E in rat rod outer segments during light damage. Investig. Ophthalmol. Vis. Sci. 27, 727733.
  • 61
    Hunt, D. F., D. T. Organisciak, H. M. Wang and R. L. C. Wu (1984) Alpha-tocopherol in the developing rat retina—a high pressure liquid chromatographic analysis. Curr. Eye Res. 3, 12811288.
  • 62
    LaVail, M. M., K. Unoki, D. Yasumura, M. T. Matthes, G. D. Yancopoulos and R. H. Steinberg (1992) Multiple growth factors, cytokines, and neurotrophins rescue photoreceptors from the damaging effects of constant light. Proc. Natl. Acad. Sci. USA 89, 1124911253.
  • 63
    Faktorovich, E. G., R. H. Steinberg, D. Yasumura, M. T. Matthes and M. M. Lavail (1992) Basic fibroblast growth factor and local injury protect photoreceptors from light damage in the rat. J. Neurosci. 12, 35543567.
  • 64
    Schremser, J. L. and T. P. Williams (1995) Rod outer segment (ROS) renewal as a mechanism for adaptation to a new intensity environment. 1. Rhodopsin levels and ROS length. Exp. Eye Res. 61, 1723.
  • 65
    Reme, C. E., U. Wolfrum, C. Imsand, F. Hafezi and T. P. Williams (1999) Photoreceptor autophagy: effects of light history on number and opsin content of degradative vacuoles. Investig. Ophthalmol. Vis. Sci. 40, 23982404.
  • 66
    Li, F., W. Cao and R. E. Anderson (2001) Protection of photoreceptor cells in adult rats from light-induced degeneration by adaptation to bright cyclic light. Exp. Eye Res. 73, 569577.
  • 67
    Organisciak, D. T., R. M. Darrow, L. Barsalou, R. A. Darrow, R. K. Krishnan, G. Kutty and B. Wiggert (1998) Light history and age-related changes in retinal light damage. Investig. Ophthalmol. Vis. Sci. 39, 11071116.
  • 68
    Noell, W. K. (1979) Effects of environmental lighting and dietary vitamin A on the vulnerability of the retina to light damage. Photochem. Photobiol. 29, 717723.
  • 69
    Harwerth, R. S. and H. G. Sperling (1975) Effects of intense visible radiation on the increment-threshold spectral sensitivity of the rhesus monkey eye. Vision Res. 15, 11931204.
  • 70
    Sperling, H. G., C. Johnson and R. S. Harwerth (1980) Differential spectral photic damage to primate cones. Vision Res. 20, 11171125.
  • 71
    Gorgels, T. and D. Vannorren (1995) Ultraviolet and green light cause different types of damage in rat retina. Investig. Ophthalmol. Vis. Sci. 36, 851863.
  • 72
    Ham, W. T., H. A. Mueller, J. J. Ruffolo, D. Guerry and R. K. Guerry (1982) Action spectrum for retinal injury from near-ultraviolet radiation in the aphakic monkey. Am. J. Ophthalmol. 93, 299306.
  • 73
    Rapp, L. M. and S. C. Smith (1992) Morphologic comparisons between rhodopsin-mediated and short-wavelength classes of retinal light damage. Investig. Ophthalmol. Vis. Sci. 33, 33673377.
  • 74
    Bush, E. M., T. G. M. F. Gorgels and D. van Norren (1999) Temporal sequence of changes in rat retina after UV-A and blue light exposure. Vision Res. 39, 12331247.
  • 75
    Rodieck, R. W. (1998) The First Steps in Seeing. Sinauer Associates, Inc., Sunderland , MA .
  • 76
    Lamb, T. D. and E. N. Pugh (2004) Dark adaptation and the retinoid cycle of vision. Prog. Retin. Eye Res. 23, 307380.
  • 77
    Kolesnikov, A. V., E. Y. Golobokova and V. I. Govardovskii (2003) The identity of metarhodopsin III. Vis. Neurosci. 20, 249265.
  • 78
    Garwin, G. G. and J. C. Saari (2000) High-performance liquid chromatography analysis of visual cycle retinoids. Methods Enzymol. 316, 313324.
  • 79
    Wenzel, A., C. E. Reme, T. P. Williams, F. Hafezi and C. Grimm (2001) The RPE65 Leu450Met variation increases retinal resistance against light-induced degeneration by slowing rhodopsin regeneration. J. Neurosci. 21, 5358.
  • 80
    Grimm, C., A. Wenzel, F. Hafezi, S. Yu, T. M. Redmond and C. E. Reme (2000) Protection of RPE65-deficient mice identifies rhodopsin as a mediator of light-induced retinal degeneration. Nat. Genet. 25, 6366.
  • 81
    Grimm, C., A. Wenzel, T. P. Williams, P. O. Rol, F. Hafezi and C. E. Reme (2001) Rhodopsin-mediated blue-light damage to the rat retina: effect of photoreversal of bleaching. Investig. Ophthalmol. Vis. Sci. 42, 497505.
  • 82
    Ruffolo, J. Jr, W. Ham, Jr, H. Mueller and J. Millen (1984) Photochemical lesions in the primate retina under conditions of elevated blood oxygen. Investig. Ophthalmol. Vis. Sci. 25, 893898.
  • 83
    Ham, W. T., H. A. Mueller, J. J. Ruffolo, J. E. Millen, S. F. Cleary, R. K. Guerry and D. Guerry (1984) Basic mechanisms underlying the production of photochemical lesions in the mammalian retina. Curr. Eye Res. 3, 165174.
  • 84
    Jaffe, G. J., A. R. Irvine, I. S. Wood, J. W. Severinghaus, G. R. Pino and C. Haugen (1988) Retinal phototoxicity from the operating microscope—the role of inspired oxygen. Ophthalmology 95, 11301141.
  • 85
    Kayatz, P., K. Heimann and U. Schraermeyer (1999) Tracing of benzidine-reactive substances in ROS, RPE and choroid after light-induced peroxidation. Graefes Arch. Clin. Exp. Ophthalmol. 237, 763774.
  • 86
    Wiegand, R. D., N. M. Giusto, L. M. Rapp and R. E. Anderson (1983) Evidence for rod outer segment lipid-peroxidation following constant illumination of the rat retina. Investig. Ophthalmol. Vis. Sci. 24, 14331435.
  • 87
    Miyagi, M., H. Sakaguchi, R. M. Darrow, L. Yan, K. A. West, K. S. Aulak, D. J. Stuehr, J. G. Hollyfield, D. T. Organisciak and J. W. Crabb (2002) Evidence that light modulates protein nitration in rat retina. Mol. Cell. Proteomics 1, 293303.
  • 88
    Ranchon, I., J. M. Gorrand, J. Cluzel, M. T. Droy-Lefaix and M. Doly (1999) Functional protection of photoreceptors from light-induced damage by dimethylthiourea and Ginkgo biloba extract. Investig. Ophthalmol. Vis. Sci. 40, 11911199.
  • 89
    Ranchon, I., S. Chen, K. Alvarez and R. E. Anderson (2001) Systemic administration of phenyl-N-tert-butylnitrone protects the retina from light damage. Investig. Ophthalmol. Vis. Sci. 42, 13751379.
  • 90
    Boulton, M., M. Rozanowska and B. Rozanowski (2001) Retinal photodamage. J. Photochem. Photobiol. B-Biol. 64, 144161.
  • 91
    Delmelle, M. (1977) Retinal damage by light: possible implication of singlet oxygen. Biophys. Struct. Mech. 3, 195198.
  • 92
    Delmelle, M. (1978) An investigation of retinal as a source of singlet oxygen. Photochem. Photobiol. 27, 721734.
  • 93
    Schadel, S. A., M. Heck, D. Maretzki, S. Filipek, D. C. Teller, K. Palczewski and K. P. Hofmann (2003) Ligand channeling within a G-protein-coupled receptor—the entry and exit of retinals in native opsin. J. Biol. Chem. 278, 2489624903.
  • 94
    Heck, M., S. A. Schadel, D. Maretzki and K. P. Hofmann (2003) Secondary binding sites of retinoids in opsin: characterization and role in regeneration. Vision Res. 43, 30033010.
  • 95
    Fishkin, N. E., J. R. Sparrow, R. Allikmets and K. Nakanishi (2005) Isolation and characterization of a retinal pigment epithelial cell fluorophore: an all-trans-retinal dimer conjugate. Proc. Natl. Acad. Sci. USA 102, 70917096.
  • 96
    Weng, J., N. L. Mata, S. M. Azarian, R. T. Tzekov, D. G. Birch and G. H. Travis (1999) Insights into the function of Rim protein in photoreceptors and etiology of Stargardt's disease from the phenotype in abcr knockout mice. Cell 98, 1323.
  • 97
    Mata, N. L., J. Weng and G. H. Travis (2000) Biosynthesis of a major lipofuscin fluorophore in mice and humans with ABCR-mediated retinal and macular degeneration. Proc. Natl. Acad. Sci. USA 97, 71547159.
  • 98
    Ben-Shabat, S., C. A. Parish, H. R. Vollmer, Y. Itagaki, N. Fishkin, K. Nakanishi and J. R. Sparrow (2002) Biosynthetic studies of A2E, a major fluorophore of retinal pigment epithelial lipofuscin. J. Biol. Chem. 277, 71837190.
  • 99
    Sparrow, J. R., N. Fishkin, J. L. Zhou, B. L. Cai, Y. P. Jang, S. Krane, Y. Itagaki and K. Nakanishi (2003) A2E, a by-product of the visual cycle. Vision Res. 43, 29832990.
  • 100
    Pepe, I. M. (2001) Recent advances in our understanding of rhodopsin and phototransduction. Prog. Retin. Eye Res. 20, 733759.
  • 101
    Okada, T., O. P. Ernst, K. Palczewski and K. P. Hofmann (2001) Activation of rhodopsin: new insights from structural and biochemical studies. Trends Biochem. Sci. 26, 318324.
  • 102
    Schroder, K., A. Pulvermuller and K. P. Hofmann (2002) Arrestin and its splice variant Arr(1-370A) (P-44)—mechanism and biological role of their interaction with rhodopsin. J. Biol. Chem. 277, 4398743996.
  • 103
    Pulvermuller, A., D. Maretzki, M. RudnickaNawrot, W. C. Smith, K. Palczewski and K. P. Hofmann (1997) Functional differences in the interaction of arrestin and its splice variant, p(), with rhodopsin44. Biochemistry 36, 92539260.
  • 104
    Palczewski, K., J. Buczylko, H. Ohguro, R. S. Annan, S. A. Carr, J. W. Crabb, M. W. Kaplan, R. S. Johnson and K. A. Walsh (1994) Characterization of a truncated form of arrestin isolated from bovine rod outer segments. Protein Sci. 3, 314324.
  • 105
    Vogel, R., F. Siebert, X. Y. Zhang, G. B. Fan and M. Sheves (2004) Formation of meta III during the decay of activated rhodopsin proceeds via meta I and not via meta II. Biochemistry 43, 94579466.
  • 106
    Niu, S. L., D. C. Mitchell and B. J. Litman (2002) Manipulation of cholesterol levels in rod disk membranes by methyl-beta-cyclodextrin. Effects on receptor activation. J. Biol. Chem. 277, 2013920145.
  • 107
    Litman, B. J. and D. C. Mitchell (1996) A role for phospholipid polyunsaturation in modulating membrane protein function. Lipids 31, S193S197.
  • 108
    Gibson, N. J. and M. F. Brown (1993) Lipid headgroup and acyl chain composition modulate the MI-MII equilibrium of rhodopsin in recombinant membranes. Biochemistry 32, 24382454.
  • 109
    Mitchell, D. C., M. Straume and B. J. Litman (1992) Role of Sn-1-saturated, Sn-2-polyunsaturated phospholipids in control of membrane-receptor conformational equilibrium—effects of cholesterol and acyl chain unsaturation on the Metarhodopsin-I-Metarhodopsin-II equilibrium. Biochemistry 31, 662670.
  • 110
    Niu, S. L., D. C. Mitchell, S. Y. Lim, Z. M. Wen, H. Y. Kim, N. Salem and B. J. Litman (2004) Reduced G protein-coupled signaling efficiency in retinal rod outer segments in response to n-3 fatty acid deficiency. J. Biol. Chem. 279, 3109831104.
  • 111
    Heck, M., S. A. Schadel, D. Maretzki, F. J. Bartl, E. Ritter, K. Palczewski and K. P. Hofmann (2003) Signaling states of rhodopsin—formation of the storage form, metarhodopsin III, from active metarhodopsin II. J. Biol. Chem. 278, 31623169.
  • 112
    Ritter, E., K. Zimmermann, M. Heck, K. P. Hofmann and F. J. Bartl (2004) Transition of rhodopsin into the active metarhodopsin II state opens a new light induced pathway linked to Schiff base isomerization. J. Biol. Chem. 279, 4810248111.
  • 113
    Blazynski, C. and S. E. Ostroy (1984) Pathways in the hydrolysis of vertebrate rhodopsin. Vision Res. 24, 459470.
  • 114
    Zimmermann, K., E. Ritter, F. J. Bartl, K. P. Hofmann and M. Martin Heck (2004) Interaction with transducin depletes Metarhodopsin III: a regulated retinal storage in visual signal transduction? J. Biol. Chem. 279, 4811248119.
  • 115
    Vogel, R., S. Ludeke, I. Radu, F. Siebert and M. Sheves (2004) Photoreactions of metarhodopsin III. Biochemistry 43, 1025510264.
  • 116
    Ernst, O. P., C. K. Meyer, E. P. Marin, P. Henklein, W. Y. Fu, T. P. Sakmar and K. P. Hofmann (2000) Mutation of the fourth cytoplasmic loop of rhodopsin affects binding of transducin and peptides derived from the carboxyl-terminal sequences of transducin alpha and gamma subunits. J. Biol. Chem. 275, 19371943.
  • 117
    Kisselev, O. G., C. K. Meyer, M. Heck, O. P. Ernst and K. P. Hofmann (1999) Signal transfer from rhodopsin to the G-protein: evidence for a two-site sequential fit mechanism. Proc. Natl. Acad. Sci. USA 96, 48984903.
  • 118
    Kuksa, V., Y. Imanishi, M. Batten, K. Palczewski and A. R. Moise (2003) Retinoid cycle in the vertebrate retina: experimental approaches and mechanisms of isomerization. Vision Res. 43, 29592981.
  • 119
    Rattner, A., P. M. Smallwood and J. Nathans (2000) Identification and characterization of all-trans-retinol dehydrogenase from photo-receptor outer segments, the visual cycle enzyme that reduces all-trans-retinal to all-trans-retinol. J. Biol. Chem. 275, 1103411043.
  • 120
    Haeseleer, F., J. Huang, L. Lebioda, J. C. Saari and K. Palczewski (1998) Molecular characterization of a novel short-chain dehydrogenase/reductase that reduces all-trans-retinal. J. Biol. Chem. 273, 2179021799.
  • 121
    Zimmerman, W. F., M. T. Yost and F. J. M. Daemen (1974) Dynamics and function of vitamin A compounds in rat retina after a small bleach of rhodopsin. Nature 250, 6667.
  • 122
    Saari, J. C., G. G. Garwin, J. P. Van Hooser and K. Palczewski (1998) Reduction of all-trans-retinal limits regeneration of visual pigment in mice. Vision Res. 38, 13251333.
  • 123
    Tsina, E., C. Chen, Y. Koutalos, P. Ala-Laurila, M. Tsacopoulos, B. Wiggert, R. K. Crouch and M. C. Cornwall (2004) Physiological and microfluorimetric studies of reduction and clearance of retinal in bleached rod photoreceptors. J. Gen. Physiol. 124, 429443.
  • 124
    Chen, C., E. Tsina, M. C. Comwall, R. K. Crouch, S. Vijayaraghavan and Y. Koutalos (2005) Reduction of all-trans retinal to all-trans retinol in the outer segments of frog and mouse rod photoreceptors. Biophys. J. 88, 22782287.
  • 125
    Poincelot, R. P., P. G. Millar, R. L. J. Kimbel and E. W. Abrahamson (1969) Lipid to protein chromophore transfer in the photolysis of visual pigments. Nature 221, 256257.
  • 126
    Anderson, R. E. and M. B. Maude (1970) Phospholipids of bovine rod outer segments. Biochemistry 9, 36243628.
  • 127
    Ahn, J., J. T. Wong and R. S. Molday (2000) The effect of lipid environment and retinoids on the ATPase activity of ABCR, the photoreceptor ABC transporter responsible for Stargardt macular dystrophy. J. Biol. Chem. 275, 2039920405.
  • 128
    Sun, H., R. S. Molday and J. Nathans (1999) Retinal stimulates ATP hydrolysis by purified and reconstituted ABCR, the photoreceptor-specific ATP-binding cassette transporter responsible for Stargardt disease. J. Biol. Chem. 274, 82698281.
  • 129
    Beharry, S., M. Zhong and R. S. Molday (2004) N-retinylidene phosphatidylethanolamine is the preferred retinoid substrate for the photoreceptor specific ABC transporter ABCA4 (ABCR). J. Biol. Chem. 279, 5397053979.
  • 130
    Mata, N. L., R. T. Tzekov, X. R. Liu, J. Weng, D. G. Birch and G. H. Travis (2001) Delayed dark-adaptation and lipofuscin accumulation in abcr+/−mice: implications for involvement of ABCR in age-related macular degeneration. Investig. Ophthalmol. Vis. Sci. 42, 16851690.
  • 131
    Shroyer, N. F., R. A. Lewis, A. N. Yatsenko and J. R. Lupski (2001) Null missense ABCR (ABCA4) mutations in a family with Stargardt disease and retinitis pigmentosa. Investig. Ophthalmol. Vis. Sci. 42, 27572761.
  • 132
    Maugeri, A., B. J. Klevering, K. Rohrschneider, A. Blankenagel, H. G. Brunner, A. F. Deutman, C. B. Hoyng and F. P. M. Cremers (2000) Mutations in the ABCA4 (ABCR) gene are the major cause of autosomal recessive cone-rod dystrophy. Am. J. Hum. Genet. 67, 960966.
  • 133
    Michaelides, M., D. M. Hunt and A. T. Moore (2003) The genetics of inherited macular dystrophies. J. Med. Genet. 40, 641650.
  • 134
    Allikmets, R. (1999) Molecular genetics of age-related macular degeneration: current status. Eur. J. Ophthalmol. 9, 255265.
  • 135
    Allikmets, R., N. Singh, H. Sun, N. E. Shroyer, A. Hutchinson, A. Chidambaram, B. Gerrard, L. Baird, D. Stauffer, A. Peiffer, A. Rattner, P. Smallwood, Y. X. Li, K. L. Anderson, R. A. Lewis, J. Nathans, M. Leppert, M. Dean and J. R. Lupski (1997) A photo-receptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat. Genet. 15, 236246.
  • 136
    Besch, D., H. Jagle, H. P. N. Scholl, M. W. Seeliger and E. Zrenner (2003) Inherited multifocal RPE-diseases: mechanisms for local dysfunction in global retinoid cycle gene defects. Vision Res. 43, 30953108.
  • 137
    Feeney-Burns, L., E. R. Berman and H. Rothman (1980) Lipofuscin of human retinal pigment epithelium. Am. J. Ophthalmol. 90, 783791.
  • 138
    Plack, P. A. and D. J. Pritchard (1969) Schiff bases formed from retinal and phosphatidylethanolamine, phosphatidylserine, ethanolamine or serine. Biochem. J. 115, 927934.
  • 139
    Saari, J. C., M. Nawrot, B. N. Kennedy, G. G. Garwin, J. B. Hurley, J. Huang, D. E. Possin and J. W. Crabb (2001) Visual cycle impairment in cellular retinaldehyde binding protein (CRALBP) knockout mice results in delayed dark adaptation. Neuron 29, 739748.
  • 140
    Imanishi, Y., V. Gerke and K. Palczewski (2004) Retinosomes: new insights into intracellular managing of hydrophobic substances in lipid bodies. J. Cell Biol. 166, 447453.
  • 141
    McBee, J. K., K. Palczewski, W. Baehr and D. R. Pepperberg (2001) Confronting complexity: the interlink of phototransduction and retinoid metabolism in the vertebrate retina. Prog. Retin. Eye Res. 20, 469529.
  • 142
    Crouch, R. K., E. S. Hazard, T. Lind, B. Wiggert, G. Chader and D. W. Corson (1992) Interphotoreceptor retinoid-binding protein and alpha-tocopherol preserve the isomeric and oxidation-state of retinol. Photochem. Photobiol. 56, 251255.
  • 143
    Batten, M. L., Y. Imanishi, T. Maeda, D. C. Tu, A. R. Moise, D. Bronson, D. Possin, R. N. Van Gelder, W. Baehr and K. Palczewski (2004) Lecithin-retinol acyltransferase is essential for accumulation of all-trans-retinyl esters in the eye and in the liver. J. Biol. Chem. 279, 1042210432.
  • 144
    Imanishi, Y., M. L. Batten, D. W. Piston, W. Baehr and K. Palczewski (2004) Noninvasive two-photon imaging reveals retinyl ester storage structures in the eye. J. Cell Biol. 164, 373383.
  • 145
    Gollapalli, D. R. and R. R. Rando (2003) Specific inactivation of isomerohydrolase activity by 11-cis-retinoids. Biochim. Biophys. Acta 1651, 93101.
  • 146
    Golczak, M., V. Kuksa, T. Maeda, A. R. Moise and K. Palczewski (2005) Positively charged retinoids are potent and selective inhibitors of the trans-cis isomerization in the retinoid (visual) cycle. Proc. Natl. Acad. Sci. USA 102, 81628167.
  • 147
    Mata, N. L., W. N. Moghrabi, J. S. Lee, T. V. Bui, R. A. Radu, J. Horwitz and G. H. Travis (2004) Rpe65 is a retinyl ester binding protein that presents insoluble substrate to the isomerase in retinal pigment epithelial cells. J. Biol. Chem. 279, 635643.
  • 148
    Gollapalli, D. R., P. Maiti and R. R. Rando (2003) RPE65 operates in the vertebrate visual cycle by stereospecifically binding all-trans-retinyl esters. Biochemistry 42, 1182411830.
  • 149
    Wolf, G. (2005) Function of the protein RPE65 in the visual cycle. Nutr. Rev. 63, 971000.
  • 150
    Xue, L. L., D. R. Gollapalli, P. Maiti, W. J. Jahng and R. R. Rando (2004) A palmitoylation switch mechanism in the regulation of the visual cycle. Cell 117, 761771.
  • 151
    Jin, M., S. Li, W. N. Moghrabi, H. Sun and G. H. Travis (2005) Rpe65 is the retinoid isomerase in bovine retinal pigment epithelium. Cell 122, 449459.
  • 152
    Katz, M. L. and T. M. Redmond (2001) Effect of RPE65 knockout on accumulation of lipofuscin fluorophores in the retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 42, 30233030.
  • 153
    Redmond, T. M., S. Yu, E. Lee, D. Bok, D. Hamasaki, N. Chen, P. Goletz, J. X. Ma, R. K. Crouch and K. Pfeifer (1998) RPE65 is necessary for production of 11-cis-vitamin A in the retinal visual cycle. Nat. Genet. 20, 344351.
  • 154
    Marlhens, F., C. Bareil, J. M. Griffoin, E. Zrenner, P. Amalric, C. Eliaou, S. Y. Liu, E. Harris, T. M. Redmond, B. Arnaud, M. Claustres and C. P. Hamel (1997) Mutations in RPE65 cause Leber's congenital amaurosis. Nat. Genet. 17, 139141.
  • 155
    Cremers, F. P. M., J. van den Hurk and A. I. den Hollander (2002) Molecular genetics of Leber congenital amaurosis. Hum. Mol. Genet. 11, 11691176.
  • 156
    Stecher, H., M. H. Gelb, J. C. Saari and K. Palczewski (1999) Preferential release of 11-cis-retinol from retinal pigment epithelial cells in the presence of cellular retinaldehyde- binding protein. J. Biol. Chem. 274, 85778585.
  • 157
    Wu, Z. P., Y. W. Yang, N. Shaw, S. Bhattacharya, L. Yan, K. West, K. Roth, N. Noy, J. Qin and J. W. Crabb (2003) Mapping the ligand binding pocket in the cellular retinaldehyde binding protein. J. Biol. Chem. 278, 1239012396.
  • 158
    Gamble, M. V., N. L. Mata, A. T. Tsin, J. R. Mertz and W. S. Blaner (2000) Substrate specificities and 13-cis-retinoic acid inhibition of human, mouse and bovine cis-retinol dehydrogenases. Biochim. Biophys. Acta 1476, 38.
  • 159
    Kim, T. S., A. Maeda, T. Maeda, C. Heinlein, N. Kedishvili, K. Palczewski and P. S. Nelson (2005) Delayed dark adaptation in 11-cis-retinol dehydrogenase-deficient mice. J. Biol. Chem. 280, 86948704.
  • 160
    Driessen, C., H. Winkens, F. Haeseleer, K. Palczewski and J. Janssen (2003) Novel targeting strategy for generating mouse models with defects in the retinoid cycle. Vision Res. 43, 30753079.
  • 161
    Haeseleer, F., G. F. Jang, Y. Imanishi, C. Driessen, M. Matsumura, P. S. Nelson and K. Palczewski (2002) Dual-substrate specificity short chain retinol dehydrogenases from the vertebrate retina. J. Biol. Chem. 277, 4553745546.
  • 162
    Jang, G. F., J. P. Van Hooser, V. Kuksa, J. K. McBee, Y. G. He, J. J. M. Janssen, C. Driessen and K. Palczewski (2001) Characterization of a dehydrogenase activity responsible for oxidation of 11-cis-retinol in the retinal pigment epithelium of mice with a disrupted RDH5 gene—a model for the human hereditary disease fundus albipunctatus. J. Biol. Chem. 276, 3245632465.
  • 163
    Kedishvili, N. Y., O. V. Chumakova, S. V. Chetyrkin, O. V. Belyaeva, E. A. Lapshina, D. W. Lin, M. Matsumura and P. S. Nelson (2002) Evidence that the human gene for prostate short-chain dehydrogenase/reductase (PSDR1) encodes a novel retinal reductase (RalR1). J. Biol. Chem. 277, 2890928915.
  • 164
    Cideciyan, A. V., F. Haeseleer, R. N. Fariss, T. S. Aleman, G. F. Jang, C. Verlinde, M. F. Marmor, S. G. Jacobson and K. Palczewski (2000) Rod and cone visual cycle consequences of a null mutation in the 11-cis-retinol dehydrogenase gene in man. Vis. Neurosci. 17, 667678.
  • 165
    Yamamoto, II., A. Simon, U. Eriksson, E. Harris, E. L. Berson and T. P. Dryja (1999) Mutations in the gene encoding 11-cis retinol dehydrogenase cause delayed dark adaptation and fundus albipunctatus. Nat. Genet. 22, 188191.
  • 166
    Nakamura, M., Y. Hotta, A. Tanikawa, H. Terasaki and Y. Miyake (2000) A high association with cone dystrophy in fundus albipunctatus caused by mutations of the RDH5 gene. Investig. Ophthalmol. Vis. Sci. 41, 39253932.
  • 167
    Nakamura, M., J. Lin and Y. Miyake (2004) Young monozygotic twin sisters with fundus albipunctatus and cone dystrophy. Arch. Ophthalmol. 122, 12031207.
  • 168
    Bonilha, V. L., S. K. Bhattacharya, K. A. West, J. S. Crabb, J. Sun, M. E. Rayborn, M. Nawrot, J. C. Saari and J. W. Crabb (2004) Support for a proposed retinoid-processing protein complex in apical retinal pigment epithelium. Exp. Eye Res. 79, 419422.
  • 169
    Nawrot, M., K. West, J. Huang, D. E. Possin, A. Bretscher, J. W. Crabb and J. C. Saari (2004) Cellular retinaldehyde-binding protein interacts with ERM-binding phosphoprotein 50 in retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 45, 393401.
  • 170
    Mata, N. L., E. T. Villazana and A. T. C. Tsin (1998) Colocalization of 11-cis retinyl esters and retinyl ester hydrolase activity in retinal pigment epithelium plasma membrane. Investig. Ophthalmol. Vis. Sci. 39, 13121319.
  • 171
    Saari, J. C., A. H. Buntmilam, D. L. Bredberg and G. G. Garwin (1984) Properties and immunocytochemical localization of three retinoid binding proteins from bovine retina. Vision Res. 24, 15951603.
  • 172
    Bunt-Milam, A. H. and J. C. Saari (1983) Immunocytochemical localization of two retinoid-binding proteins in vertebrate retina. J. Cell Biol. 97, 703712.
  • 173
    Gonzalez-Fernandez, F. (2003) Interphotoreceptor retinoid-binding protein—an old gene for new eyes. Vision Res. 43, 30213036.
  • 174
    Fedorovich, I. B., E. M. Semenova, K. Grant, C. A. Converse and M. A. Ostrovsky (2000) Photosensitized light-induced damage of IRBP (interphotoreceptor retinoid-binding protein): effects on binding properties. Curr. Eye Res. 21, 975980.
  • 175
    Jacobson, S. G., A. V. Cideciyan, C. M. Kemp, V. C. Sheffield and E. M. Stone (1996) Photoreceptor function in heterozygotes with insertion or deletion mutations in the RDS gene. Investig. Ophthalmol. Vis. Sci. 37, 16621674.
  • 176
    Kemp, C. M., S. G. Jacobson, A. V. Cideciyan, A. E. Kimura, V. C. Sheffield and E. M. Stone (1994) RDSA gene-mutations causing retinitis-pigmentosa or macular degeneration lead to the same abnormality in photoreceptor function. Investig. Ophthalmol. Vis. Sci. 35, 31543162.
  • 177
    Wroblewski, J. J., J. A. Wells, A. Eckstein, F. Fitzke, C. Jubb, T. J. Keen, C. Inglehearn, S. Bhattacharya, G. B. Arden, M. Jay and A. C. Bird (1994) Macular dystrophy associated with mutations at codon-172 in the human retinal degeneration slow gene. Ophthalmology 101, 1222.
  • 178
    Wells, J., J. Wroblewski, J. Keen, C. Inglehearn, C. Jubb, A. Eckstein, M. Jay, G. Arden, S. Bhattacharya, F. Fitzke and A. Bird (1993) Mutations in the human retinal degeneration slow (Rds) gene can cause either retinitis-pigmentosa or macular dystrophy. Nat. Genet. 3, 213218.
  • 179
    Mata, N. L., R. A. Radu, R. S. Clemmons and G. H. Travis (2002) Isomerization and oxidation of vitamin a in cone-dominant retinas: a novel pathway for visual-pigment regeneration in daylight. Neuron 36, 6980.
  • 180
    Goldstein, E. B. (1970) Cone pigment regeneration in the isolated frog retina. Vision Res. 10, 10651968.
  • 181
    Hood, D. C. and P. A. Hock (1973) Recovery of cone receptor activity in the frog's isolated retina. Vision Res. 13, 19431951.
  • 182
    Saari, J. C., L. Bredberg and G. G. Garwin (1982) Identification of the endogenous retinoids associated with three cellular retinoid binding proteins from bovine retina and retinal pigment epithelium. J. Biol. Chem. 257, 33293333.
  • 183
    Bok, D., D. E. Ong and F. Chytil (1984) Immunocytochemical localization of cellular retinol binding protein in the rat retina. Investig. Ophthalmol. Vis. Sci. 25, 877883.
  • 184
    Saari, J. C. and D. L. Bredberg (1987) Photochemistry and stereoselectivity of cellular retinaldehyde-binding protein from bovine retina. J. Biol. Chem. 262, 76187622.
  • 185
    Das, S. R., N. Bhardwaj, H. Kjeldbye and P. Gouras (1992) Muller cells of chicken retina synthesize 11-cis-retinol. Biochem. J. 285, 907913.
  • 186
    Znoiko, S. L., R. K. Crouch, G. Moiseyev and J. X. Ma (2002) Identification of the RPE65 protein in mammalian cone photo-receptors. Investig. Ophthalmol. Vis. Sci. 43, 16041609.
  • 187
    Jones, G. J., A. Fein, E. F. Macnichol and M. C. Cornwall (1993) Visual pigment bleaching in isolated salamander retinal cones—microspectrophotometry and light adaptation. J. Gen. Physiol. 102, 483502.
  • 188
    Jin, J., G. J. Jones and M. C. Cornwall (1994) Movement of retinal along cone and rod photoreceptors. Vis. Neurosci. 11, 389399.
  • 189
    Perrault, I., S. Hanein, S. Gerber, F. Barbet, D. Ducroq, H. Dollfus, C. Hamel, J. L. Dufier, A. Munnich, J. Kaplan and J. M. Rozet (2004) Retinal dehydrogenase 12 (RDH12) mutations in Leber congenital amaurosis. Am. J. Hum. Genet. 75, 639646.
  • 190
    Janecke, A. R., D. A. Thompson, G. Utermann, C. Becker, C. A. Hubner, E. Schmid, C. L. McHenry, A. R. Nair, F. Ruschendorf, J. Heckenlively, B. Wissinger, P. Nurnberg and A. Gal (2004) Mutations in RDH12 encoding a photoreceptor cell retinol dehydrogenase cause childhood-onset severe retinal dystrophy. Nat. Genet. 36, 850854.
  • 191
    Cideciyan, A. V., T. S. Aleman, M. Swider, S. B. Schwartz, J. D. Steinberg, A. J. Brucker, A. M. Maguire, J. Bennett, E. M. Stone and S. G. Jacobson (2004) Mutations in ABCA4 result in accumulation of lipofuscin before slowing of the retinoid cycle: a reappraisal of the human disease sequence. Hum. Mol. Genet. 13, 525534.
  • 192
    Bridges, C. D. B., R. A. Alvarez and S. L. Fong (1982) Vitamin A in human eyes—amount, distribution, and composition. Investig, Ophthalmol. Vis. Sci. 22, 706714.
  • 193
    Radu, R. A., J. Hu, W. N. Moghrabi, N. L. Mata, D. Bok and G. H. Travis (2004) Light-dependent regulation of the visual cycle by non-photoreceptor opsins in the RPE cells. Investig. Ophthalmol. Vis. Sci. 45, E-Abstract 1246.
  • 194
    Hao, W. S. and H. K. W. Fong (1999) The endogenous chromophore of retinal G protein-coupled receptor opsin from the pigment epithelium. J. Biol. Chem. 274, 60856090.
  • 195
    Hao, W. S. and H. K. W. Fong (1996) Blue and ultraviolet light-absorbing opsin from the retinal pigment epithelium. Biochemistry 35, 62516256.
  • 196
    Chen, P., T. D. Lee and H. K. W. Fong (2001) Interaction of 11-cis-retinol dehydrogenase with the chromophore of retinal G proteincoupled receptor opsin. J. Biol. Chem. 276, 2109821104.
  • 197
    Chen, P., W. S. Hao, L. Rife, X. P. Wang, D. W. Shen, J. Chen, T. Ogden, G. B. Van Boemel, L. Y. Wu, M. Yang and H. K. W. Fong (2001) A photic visual cycle of rhodopsin regeneration is dependent on Rgr. Nat. Genet. 28, 256260.
  • 198
    Maeda, T., J. P. Van Hooser, C. Driessen, S. Filipek, J. J. M. Janssen and K. Palczewski (2003) Evaluation of the role of the retinal G protein-coupled receptor (RGR) in the vertebrate retina in vivo. J. Neurochem. 85, 944956.
  • 199
    Van Hooser, J. P., Y. Liang, T. Maeda, V. Kuksa, G. F. Jang, Y. G. He, F. Rieke, II. K. W. Fong, P. B. Detwiler and K. Palczewski (2002) Recovery of visual functions in a mouse model of Leber congenital amaurosis. J. Biol. Chem. 277, 1917319182.
  • 200
    Sun, H., D. J. Gilbert, N. G. Copeland, N. A. Jenkins and J. Nathans (1997) Peropsin, a novel visual pigment-like protein located in the apical microvilli of the retinal pigment epithelium. Proc. Natl. Acad. Sci. USA 94, 98939898.
  • 201
    Liu, J. H., Y. Itagaki, S. Ben-Shabat, K. Nakanishi and J. R. Sparrow (2000) The biosynthesis of A2E, a fluorophore of aging retina, involves the formation of the precursor, A2-PE, in the photo-receptor outer segment membrane. J. Biol. Chem. 275, 2935429360.
  • 202
    Lamb, L. E. and J. D. Simon (2004) A2E: a component of ocular lipofuscin. Photochem. Photobiol. 79, 127136.
  • 203
    Bazan, H. E. P., N. G. Bazan, L. Feeneyburns and E. R. Berman (1990) Lipids in human lipofuscin-enriched subcellular-fractions of 2 age populations—comparison with rod outer segments and neural retina. Investig. Ophthalmol. Vis. Sci. 31, 14331443.
  • 204
    Poincelot, R. P., P. G. Millar, R. L. J. Kimbel and E. W. Abrahamson (1970) Determination of the chromophoric binding site in native bovine rhodopsin. Biochemistry 9, 18091816.
  • 205
    Eldred, G. E. and M. R. Lasky (1993) Retinal age pigments generated by self-assembling lysosomotropic detergents. Nature 361, 724726.
  • 206
    Sparrow, J. R., C. A. Parish, M. Hashimoto and K. Nakanishi (1999) A2E, a lipofuscin fluorophore, in human retinal pigmented epithelial cells in culture. Investig. Ophthalmol. Vis. Sci. 40, 29882995.
  • 207
    Delori, F. C., C. K. Dorey, G. Staurenghi, O. Arend, D. G. Goger and J. J. Weiter (1995) In vivo fluorescence of the ocular fundus exhibits retinal pigment epithelium lipofuscin characteristics. Investig. Ophthalmol. Vis. Sci. 36, 718729.
  • 208
    Delori, F. C., D. G. Goger and C. K. Dorey (2001) Age-related accumulation and spatial distribution of lipofuscin in RPE of normal subjects. Investig. Ophthalmol. Vis. Sci. 42, 18551866.
  • 209
    Kim, S. R., N. Fishkin, J. Kong, K. Nakanishi, R. Allikmets and J. R. Sparrow (2004) Rpe65 Leu450Met variant is associated with reduced levels of the retinal pigment epithelium lipofuscin fluorophores A2E and iso-A2E. Proc. Natl. Acad. Sci. USA 101, 1166811672.
  • 210
    Gollapalli, D. R. and R. R. Rando (2004) The specific binding of retinoic acid to RPE65 and approaches to the treatment of macular degeneration. Proc. Natl. Acad. Sci. USA. 101, 1003010035.
  • 211
    Law, W. C. and R. R. Rando (1989) The molecular basis of retinoic acid induced night blindness. Biochem. Biophys. Res. Commun. 161, 825829.
  • 212
    Radu, R. A., N. L. Mata, S. Nusinowitz, X. R. Liu, P. A. Sieving and G. H. Travis (2003) Treatment with isotretinoin inhibits lipofuscin accumulation in a mouse model of recessive Stargardt's macular degeneration. Proc. Natl. Acad. Sci. USA 100, 47424747.
  • 213
    Becker, R. S. (1988) The visual process—photophysics and photo-isomerization of model visual pigments and the primary reaction. Photochem. Photobiol. 48, 369399.
  • 214
    Bensasson, R. V., E. J. Land and T. G. Truscott (1983) Flash Photolysis and Pulse Radiolysis. Contributions to the Chemistry of Biology and Medicine. Pergamon Press, Oxford .
  • 215
    Dillon, J., E. R. Gaillard, P. Bilski, C. F. Chignell and K. J. Reszka (1996) The photochemistry of the retinoids as studied by steady-state and pulsed methods. Photochem. Photobiol. 63, 680685.
  • 216
    Das, P. K. and R. S. Becker (1979) Triplet state photophysical properties and intersystem crossing quantum efficiencies of homologues of retinals in various solvents. J. Am. Chem. Soc. 101, 63486353.
  • 217
    Truscott, T. G., E. J. Land and A. Sykes (1973) The in vitro photochemistry of biological molecules-III. Absorption spectra, life-times and rates of oxygen quenching of the triplet states of b-carotene, retinal and related polyenes. Photochem. Photobiol. 17, 4351.
  • 218
    Rozanowska, M., J. Wessels, M. Boulton, J. M. Burke, M. A. J. Rodgers, T. G. Truscott and T. Sarna (1998) Blue light-induced singlet oxygen generation by retinal lipofuscin in non-polar media. Free Radic. Biol. Med. 24, 11071112.
  • 219
    Harper, W. S. and E. R. Gaillard (2001) Studies of all-trans-retinal as a photooxidizing agent. Photochem. Photobiol. 73, 7176.
  • 220
    Pawlak, A., M. Wrona, M. Rozanowska, M. Zareba, L. E. Lamb, J. Roberts, J. D. Simon and T. Sarna (2003) Comparison of the aerobic photoreactivity of A2E with its precursor retinal. Photochem. Photobiol. 77, 253258.
  • 221
    Fisher, M. M. and K. Weiss (1974) Laser photolysis of retinal and its protonated and unprotonated N-butylamine schiff base. Photochem. Photobiol. 20, 423432.
  • 222
    Harper, W. S. and E. R. Gaillard (2003) A photochemical study of (E,E,E,E)-2-9-(2-hydroxyethyl)imino3,7-dimethyl-1,3,5,7-decatrien-1-yl-1,3,3- trimethylcyclohexene, a derivative of all-trans-retinal and ethanolamine. Photochem. Photobiol. 78, 298305.
  • 223
    Kim, J. E., M. J. Tauber and R. A. Mathies (2001) Wavelength dependent cis-trans isomerization in vision. Biochemistry 40, 1377413778.
  • 224
    Rozanowska, M. B., B. Rozanowski, A. Pawlak, M. Zareba, M. E. Boulton and T. Sama (2003) Phosphatidylethanolamine prevents retinal photodamage. In 10th Congress of the European Society for Photobiology Programme and Book of Abstracts (Edited by H.Honingsmann), p. 48 Vienna, Austria .
  • 225
    Crabb, J. W., Z. Q. Nie, Y. Chen, J. D. Hulmes, K. A. West, J. T. Kapron, S. E. Ruuska, N. Noy and J. C. Saari (1998) Cellular retinaldehyde-binding protein ligand interactions—GLN-210 and LYS-221 are in the retinoid binding pocket. J. Biol. Chem. 273, 2071220720.
  • 226
    Pogozheva, I. D., I. B. Fedorovich, M. A. Ostrovsky and N. M. Emanuel (1981) Photodamage of rhodopsin molecule—oxidation of SH-group. Biofizika 26, 398403.
  • 227
    Sun, H. and J. Nathans (2001) ABCR, the ATP-binding cassette transporter responsible for Stargardt macular dystrophy, is an efficient target of all-trans-retinal-mediated photooxidative damage in vitro—implications for retinal disease. J. Biol. Chem. 276, 1176611774.
  • 228
    Ablonczy, Z., D. R. Knapp, R. Darrow, D. T. Organisciak and R. K. Crouch (2000) Mass spectrometric analysis of rhodopsin from light damaged rats. Mol. Vis. 6, 109115.
  • 229
    Murata, M. and S. Kawanishi (2000) Oxidative DNA damage by vitamin A and its derivative via superoxide generation. J. Biol. Chem. 275, 20032008.
  • 230
    Rozanowski, B., M. B. Rozanowska and M. E. Boulton (2003) Toxicity of all-trans retinal to the retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 44, 1643.
  • 231
    Delatour, T., J. Favrot, M. H. Baron, J. Belloc and C. De Loze (1982) Photochemical evolution of trans-retinal and trans-n-retinylidene n-butylamine under laser beam irradiation. Chem. Phys. Lett. 87, 379383.
  • 232
    Rozanowska, M. B., B. Rozanowski, A. Pawlak, T. Sarna and J. D. Simon (2003) Peroxidized docosahexaenoic fatty acid as a photo-generator of reactive oxygen species in the retina. Investig. Ophthalmol. Vis. Sci. 44, E-Abstract 396.
  • 233
    Rozanowski, B., M. E. Boulton and M. B. Rozanowska (2004) Action spectra of photo-oxidation for bleached and dark-adapted photo-receptor outer segments. Investig. Ophthalmol. Vis. Sci. 44, E-Abstract 717.
  • 234
    Organisciak, D. T., A. Xie, H. M. Wang, Y. L. Jiang, R. M. Darrow and L. A. Donoso (1991) Adaptive-changes in visual cell transduction protein-levels—effect of light. Exp. Eye Res. 53, 773779.
  • 235
    Williams, T. P., A. Squitieri, R. P. Henderson and J. P. P. Webbers (1999) Reciprocity between light intensity and rhodopsin concentration across the rat retina. J. Physiol. 516, 869874.
  • 236
    Kaldi, I., R. E. Martin, H. Huang, R. S. Brush, K. A. Morrison and R. E. Anderson (2003) Bright cyclic rearing protects albino mouse retina against acute light-induced apoptosis. Mol. Vis. 9, 337344.
  • 237
    Bush, R. A., C. E. Reme and A. Malnoe (1991) Light damage in the rat retina—the effect of dietary deprivation of n-3 fatty-acids on acute structural alterations. Exp. Eye Res. 53, 741752.
  • 238
    Bush, R. A., A. Malnoe, C. E. Reme and T. P. Williams (1994) Dietary deficiency of n-3 fatty-acids alters rhodopsin content and function in the rat retina. Investig. Ophthalmol. Vis. Sci. 35, 91100.
  • 239
    Penn, J. S. and R. E. Anderson (1987) Effect of light history on rod outer segment membrane composition in the rat. Exp. Eye Res. 44, 767778.
  • 240
    Sokolov, M., A. L. Lyubarsky, K. J. Strissel, A. B. Savchenko, V. I. Govardovskii, E. N. Pugh and V. Y. Arshavsky (2002) Massive light-driven translocation of transducin between the two major compartments of rod cells: a novel mechanism of light adaptation. Neuron 34, 95106.
  • 241
    Danciger, M., M. T. Matthes, D. Yasamura, N. B. Akhmedov, T. Rickabaugh, S. Gentleman, T. M. Redmond, M. M. La Vail and D. B. Farber (2000) A QTL on distal Chromosome 3 that influences the severity of light-induced damage to mouse photoreceptors. Mamm. Genome 11, 422427.
  • 242
    Wenzel, A., C. Grimm, M. Samardzija and C. E. Reme (2003) The genetic modifier RPE65 Leu(450): effect on light damage susceptibility in c-Fos-deficient mice. Investig. Ophthalmol. Vis. Sci. 44, 27982802.
  • 243
    Nusinowitz, S., L. Nguyen, R. Radu, Z. Kashani, D. Farber and M. Danciger (2003) Electroretinographic evidence for altered photo-transduction gain and slowed recovery from photobleaches in albino mice with a MET450 variant in RPE65. Exp. Eye Res. 77, 627638.
  • 244
    Sparrow, J. R. (2003) Therapy for macular degeneration: insights from acne. Proc. Natl. Acad. Sci. USA 100, 43534354.
  • 245
    Sieving, P. A., P. Chaudhry, M. Kondo, M. Provenzano, D. Wu, T. J. Carlson, R. A. Bush and D. A. Thompson (2001) Inhibition of the visual cycle in vivo by 13-cis retinoic acid protects from light damage and provides a mechanism for night blindness in isotretinoin therapy. Proc. Natl. Acad. Sci. USA 98, 18351840.
  • 246
    Ishizawa, Y., R. Pidikiti, P. A. Liebman and R. G. Eckenhoff (2002) G protein-coupled receptors as direct targets of inhaled anesthetics. Mol. Pharmacol. 61, 945952.
  • 247
    Keller, C., C. Grimm, A. Wenzel, F. Hafezi and C. E. Reme (2001) Protective effect of halothane anesthesia on retinal light damage: inhibition of metabolic rhodopsin regeneration. Investig. Ophthalmol. Vis. Sci. 42, 476480.
  • 248
    Rapp, L. M. and A. J. Ghalayini (1999) Influence of UVA light stress on photoreceptor cell metabolism: decreased rates of rhodopsin regeneration and opsin synthesis. Exp. Eye Res. 68, 757764.
  • 249
    Noorwez, S. M., V. Kuksa, Y. Imanishi, L. Zhu, S. Filipek, K. Palczewski and S. Kaushal (2003) Pharmacological chaperone-mediated in vivo folding and stabilization of the P23H-opsin mutant associated with autosomal dominant retinitis pigmentosa. J. Biol. Chem. 278, 1444214450.
  • 250
    Katz, M. L., C. L. Gao and L. M. Rice (1999) Long-term variations in cyclic light intensity and dietary vitamin a intake modulate lipofuscin content of the retinal pigment epithelium. J. Neurosci. Res. 57, 106116.
  • 251
    Fite, K. V., L. Bengston and B. Donaghey (1993) Experimental light damage increases lipofuscin in the retinal pigment epithelium of Japanesequail (Coturnix coturnix Japonica). Exp. Eye Res. 57, 449460.
  • 252
    Schutt, F., B. Ueberle, M. Schnolzer, F. G. Holz and J. Kopitz (2002) Proteome analysis of lipofuscin in human retinal pigment epithelial cells. FEBS Lett. 528, 217221.
  • 253
    Eldred, G. E. and M. L. Katz (1988) Fluorophores of the human retinal pigment epithelium—separation and spectral characterization. Exp. Eye Res. 47, 7186.
  • 254
    Parish, C. A., M. Hashimoto, K. Nakanishi, J. Dillon and J. Sparrow (1998) Isolation and one-step preparation of A2E and iso-A2E, fluorophores from human retinal pigment epithelium. Proc. Natl. Acad. Sci. USA 95, 1460914613.
  • 255
    Eldred, G. E. (1998) Lipofuscin and other lysosomal storage deposits in the retinal pigment epithelium. In The Retinal Pigment Epithelium Function and Disease (Edited by M. F.Marmor and T. J.Wolfensberger), pp. 651668. Oxford University Press, New York .
  • 256
    Delaey, J. J. and C. Verougstraete (1995) Hyperlipofuscinosis and subretinal fibrosis in Stargardts disease. Retin.J. Retin. Vitr. Dis. 15, 399406.
  • 257
    Bimbach, C. D., M. Jarvelainen, D. E. Possin and A. H. Milam (1994) Histopathology and immunocytochemistry of the neurosensory retina in fundus flavimaculatus. Ophthalmology 101, 12111219.
  • 258
    Curcio, C. A. (2001) Photoreceptor topography in ageing and age-related maculopathy. Eye 15, 376383.
  • 259
    Roth, F., A. Bindewald and F. G. Holz (2004) Key pathophysiologic pathways in age-related macular disease. Graefes Arch. Clin. Exp. Ophthalmol. 242, 710716.
  • 260
    Kliffen, M., T. L. VanderSchaft, C. M. Mooy and P. de Jong (1997) Morphologic changes in age-related maculopathy. Microsc. Res. Tech. 36, 106122.
  • 261
    Lorenz, B. and M. N. Preising (2005) Best's disease. Overview of pathology and its causes. Ophthalmologe 102, 111115.
  • 262
    Kolb, H. and P. Gouras (1974) Electron microscopic observations of human retinitis pigmentosa, dominantly inherited. Investig. Ophthalmol. 13, 487498.
  • 263
    Bergsma, D. R., B. N. Wiggert, M. Funahashi, T. Kuwabara and C. J. Chader (1977) Vitamin A receptors in normal and dystrophic human retina. Nature 265, 6667.
  • 264
    Young, R. W. (1987) Pathophysiology of age-related macular degeneration. Surv. Ophthalmol. 31, 291306.
  • 265
    Dorey, C. K., G. Wu, D. Ebenstein, A. Garsd and J. J. Weiter (1989) Cell loss in the aging retina—relationship to lipofuscin accumulation and macular degeneration. Investig. Ophthalmol. Vis. Sci. 30, 16911699.
  • 266
    Taylor, A., P. F. Jacques and C. K. Dorey (1993) Oxidation and aging—impact on vision. Toxicol. Ind. Health 9, 349371.
  • 267
    Kennedy, C. J., P. E. Rakoczy and I. J. Constable (1995) Lipofuscin of the retinal pigment epithelium: a review. Eye 9, 763771.
  • 268
    Klein, R., B. E. K. Klein, S. C. Tomany, S. M. Meuer and G. H. Huang (2002) Ten-year incidence and progression of age-related maculopathy. Ophthalmology 109, 17671779.
  • 269
    Katz, M. L. (2002) Potential role of retinal pigment epithelial lipofuscin accumulation in age-related macular degeneration. Arch. Gerontol. Geriatr. 34, 359370.
  • 270
    Boulton, M., M. Rozanowska, B. Rozanowski and T. Wess (2004) The photoreactivity of ocular lipofuscin. Photochem. Photobiol. Sci. 3, 759764.
  • 271
    Eagle, R. C. J., A. C. Lucier, V. B. J. Benardino and M. Yanoff (1980) Retinal pigment epithelial abnormalities in fundus flavimaculatus: a light and electron microscopic study. Ophthalmology 87, 11891200.
  • 272
    Winkler, B. S., M. E. Boulton, J. D. Gottsch and P. Sternberg (1999) Oxidative damage and age-related macular degeneration. Mol. Vis. 5, U50U60.
  • 273
    Beatty, S., H. H. Koh, D. Henson and M. Boulton (2000) The role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 45, 115134.
  • 274
    Rozanowska, M., J. Jarvis-Evans, W. Korytowski, M. E. Boulton, J. M. Burke and T. Sarna (1995) Blue light-induced reactivity of retinal age pigment—in vitro generation of oxygen reactive species. J. Biol. Chem. 270, 1882518830.
  • 275
    Boulton, M., A. Dontsov, J. Jarvis-Evans, M. Ostrovsky and D. Svistunenko (1993) Lipofuscin is a photoinducible free-radical generator. J. Photochem. Photobiol. B-Biol. 19, 201204.
  • 276
    Wassell, J., S. Davies, W. Bardsley and M. Boulton (1999) The photoreactivity of the retinal age pigment lipofuscin. J. Biol. Chem. 274, 2382823832.
  • 277
    Dontsov, A. E., R. D. Glickman and M. A. Ostrovsky (1999) Retinal pigment epithelium pigment granules stimulate the photo-oxidation of unsaturated fatty acids. Free Radic. Biol. Med. 26, 14361446.
  • 278
    Rozanowska, M., W. Korytowski, B. Rozanowski, C. Skumatz, M. E. Boulton, J. M. Burke and T. Sarna (2002) Photoreactivity of aged human RPE melanosomes: a comparison with lipofuscin. Investig. Ophthalmol. Vis. Sci. 43, 20882096.
  • 279
    Shamsi, F. A. and M. Boulton (2001) Inhibition of RPE lysosomal and antioxidant activity by the age pigment lipofuscin. Investig. Ophthalmol. Vis. Sci. 42, 30413046.
  • 280
    Reszka, K., G. E. Eldred, R. H. Wang, C. Chignell and J. Dillon (1995) The photochemistry of human retinal lipofuscin as studied by EPR. Photochem. Photobiol. 62, 10051008.
  • 281
    Gaillard, E. R., S. J. Atherton, G. Eldred and J. Dillon (1995) Photophysical studies on human retinal lipofuscin. Photochem. Photobiol. 61, 448453.
  • 282
    McLean, A. J., D. J. McGarvey, T. G. Truscott, C. R. Lambert and E. J. Land (1990) Effect of oxygen-enhanced intersystem crossing on the observed efficiency of formation of singlet oxygen. J. Chem. Soc.-Faraday Trans. 86, 30753080.
  • 283
    Rozanowska, M., A. Pawlak, B. Rozanowski, C. Skumatz, M. Zareba, M. E. Boulton, J. M. Burke, T. Sarna and J. D. Simon (2004) Age-related changes in the photoreactivity of retinal lipofuscin granules: role of chloroform-insoluble components. Investig. Ophthalmol. Vis. Sci. 45, 10521060.
  • 284
    Davies, S., M. H. Elliott, E. Floor, T. G. Truscot, M. Zareba, T. Sarna, F. A. Sharni and M. E. Boulton (2001) Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells. Free Radic. Biol. Med. 31, 256265.
  • 285
    Feeney-Burns, L., E. S. Hilderbrand and S. Eldridge (1984) Aging human RPR—morphometric analysis of macular, equatorial, and peripheral cells. Investig. Ophthalmol. Vis. Sci. 25, 195200.
  • 286
    Zinn, K. M. and J. V. Benjamin-Henkind (1979) The retinal pigment epithelium. In Anatomy of the Human Retinal Pigment Epithelium (Edited by K. M.Zinn and M. F.Marmor), pp. 331. Harvard University Press, Cambridge .
  • 287
    Weiter, J. J., F. C. Delori, G. L. Wing and K. A. Fitch (1986) Retinal pigment epithelial lipofuscin and melanin and choroidal melanin in human eyes. Investig. Ophthalmol. Vis. Sci. 27, 145152.
  • 288
    Wing, G. L., G. C. Blanchard and J. J. Weiter (1978) The topography and age relationship of lipofuscin concentration in the retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 17, 601607.
  • 289
    Roberts, J. E., B. M. Kukielczak, D. N. Hu, D. S. Miller, P. Bilski, R. H. Sik, A. G. Motten and C. F. Chignell (2002) The role of A2E in prevention or enhancement of light damage in human retinal pigment epithelial cells. Photochem. Photobiol. 75, 184190.
  • 290
    Sparrow, J. R. and M. Boulton (2005) RPE lipofuscin and its role in retinal-pathobiology. Exp. Eye Res. 80, 595606.
  • 291
    Schutt, F., M. Bergmann, F. G. Holz and J. Kopitz (2002) Isolation of intact lysosomes from human RPE cells and effects of A2-E on the integrity of the lysosomal and other cellular membranes. Graefes Arch. Clin. Exp. Ophthalmol. 240, 983988.
  • 292
    De, S. and T. P. Sakmar (2002) Interaction of A2E with model membranes. Implications to the pathogenesis of age-related macular degeneration. J. Gen. Physiol. 120, 147157.
  • 293
    Bergmann, M., F. Schutt, F. G. Holz and J. Kopitz (2004) Inhibition of the ATP-driven proton pump in RPE lysosomes by the major lipofuscin fluorophore A2-E may contribute to the pathogenesis of age-related macular degeneration. FASEB J. 18, U450U469.
  • 294
    Shaban, H., P. Gazzotti and C. Richter (2001) Cytochrome c oxidase inhibition by N-retinyl-N-retinylidene ethanolamine, a compound suspected to cause age-related macula degeneration. Arch. Biochem. Biophys. 394, 111116.
  • 295
    Suter, M., C. Reme, C. Grimm, A. Wenzel, M. Jaattela, P. Esser, N. Kociok, M. Leist and C. Richter (2000) Age-related macular degeneration—the lipofuscin component N- retinyl-N-retinylidene ethanolamine detaches proapoptotic proteins from mitochondria and induces apoptosis in mammalian retinal pigment epithelial cells. J. Biol. Chem. 275, 3962539630.
  • 296
    Gao, B., A. Wenzel, C. Grimm, S. R. Vavricka, D. Benke, P. J. Meier and C. E. Reme (2002) Localization of organic anion transport protein 2 in the apical region of rat retinal pigment epithelium. Investig. Ophthalmol. Vis. Sci. 43, 510514.
  • 297
    Sparrow, J. R., K. Nakanishi and C. A. Parish (2000) The lipofuscin fluorophore A2E mediates blue light-induced damage to retinal pigmented epithelial cells. Investig. Ophthalmol. Vis. Sci. 41, 19811989.
  • 298
    Sparrow, J. R. and B. L. Cai (2001) Blue light-induced apoptosis of A2E-containing RPE: involvement of caspase-3 and protection by bcl-2. Investig. Ophthalmol. Vis. Sci. 42, 13561362.
  • 299
    Sparrow, J. R., J. L. Zhou and B. L. Cai (2003) DNA is a target of the photodynamic effects elicited in A2E-laden RPE by blue-light illumination. Investig. Ophthalmol. Vis. Sci. 44, 22452251.
  • 300
    Sparrow, J. R., J. Zhou, S. Ben-Shabat, H. Vollmer, Y. Itagaki and K. Nakanishi (2002) Involvement of oxidative mechanisms in blue-light-induced damage to A2E-laden RPE. Investig. Ophthalmol. Vis. Sci. 43, 12221227.
  • 301
    Shaban, H., C. Borras, J. Vina and C. Richter (2002) Phosphatidylglycerol potently protects human retinal pigment epithelial cells against apoptosis induced by A2E, a compound suspected to cause age-related macula degeneration. Exp. Eye Res. 75, 99108.
  • 302
    Holz, F. G., F. Schutt, J. Kopitz, G. E. Eldred, F. E. Kruse, H. E. Volcker and M. Cantz (1999) Inhibition of lysosomal degradative functions in RPE cells by a retinoid component of lipofuscin. Investig. Ophthalmol. Vis. Sci. 40, 737743.
  • 303
    Schutt, F., S. Davies, J. Kopitz, F. G. Holz and M. E. Boulton (2000) Photodamage to human RPE cells by A2-E, a retinoid component of lipofuscin. Investig. Ophthalmol. Vis. Sci. 41, 23032308.
  • 304
    Finnemann, S. C., L. W. Leung and E. Rodriguez-Boulan (2002) The lipofuscin component A2E selectively inhibits phagolysosomal degradation of photoreceptor phospholipid by the retinal pigment epithelium. Proc. Natl. Acad. Sci. USA 99, 38423847.
  • 305
    Bermann, M., F. Schutt, F. G. Holz and J. Kopitz (2001) Does A2E, a retinoid component of lipofuscin and inhibitor of lysosomal degradative functions, directly affect the activity of lysosomal hydrolases? Exp. Eye Res. 72, 191195.
  • 306
    Lamb, L. E., T. Ye, N. M. Haralampus-Grynaviski, T. R. Williams, A. Pawlak, T. Sarna and J. D. Simon (2001) Primary photophysical properties of A2E in solution. J. Phys. Chem. B. 105, 1150711512.
  • 307
    Kanofsky, J. R., P. D. Sima and C. Richter (2003) Singlet-oxygen generation from A2E. Photochem. Photobiol. 77, 235242.
  • 308
    Pawlak, A., M. Rozanowska, M. Zareba, L. E. Lamb, J. D. Simon and T. Sarna (2002) Action spectra for the photoconsumption of oxygen by human ocular lipofuscin and lipofuscin extracts. Arch. Biochem. Biophys. 403, 5962.
  • 309
    Haralampus-Grynaviski, N. M., L. E. Lamb, C. M. R. Clancy, C. Skumatz, J. M. Burke, T. Sarna and J. D. Simon (2003) Spectroscopic and morphological studies of human retinal lipofuscin granules. Proc. Natl. Acad. Sci. USA 100, 31793184.
  • 310
    Cantrell, A., D. J. McGarvey, J. Roberts, T. Sarna and T. G. Truscott (2001) Photochemical studies of A2-E. J. Photochem. Photobiol. B-Biol. 64, 162165.
  • 311
    Ragauskaite, L., R. C. Heckathorn and E. R. Gaillard (2001) Environmental effects on the photochemistry of A2-E, a component of human retinal lipofuscin. Photochem. Photobiol. 74, 483488.
  • 312
    Ben-Shabat, S., Y. Itagaki, S. Jockusch, J. R. Sparrow, N. J. Turro and K. Nakanishi (2002) Formation of a nonaoxirane from A2E, a lipofuscin fluorophore related to macular degeneration, and evidence of singlet oxygen involvement. Angew. Chem. Int. Ed. 41, 814817.
  • 313
    Gaillard, E. R., L. B. Avalle, L. M. M. Keller, Z. Wang, K. J. Reszka and J. P. Dillon (2004) A mechanistic study of the photooxidation of A2E, a component of human retinal lipofuscin. Exp. Eye Res. 79, 313319.
  • 314
    Dillon, J., Z. Wang, L. B. Avalle and E. R. Gaillard (2004) The photochemical oxidation of A2E results in the formation of a 5,8,5′,8′-bis-furanoid oxide. Exp. Eye Res. 79, 537542.
  • 315
    Sparrow, J. R., H. R. Vollmer-Snarr, J. L. Zhou, Y. P. Jang, S. Jockusch, Y. Itagaki and K. Nakanishi (2003) A2E-epoxides damage DNA in retinal pigment epithelial cells—vitamin E and other antioxidants inhibit A2E-epoxide formation. J. Biol. Chem. 278, 1820718213.
  • 316
    Avalle, L. B., Z. Wang, J. P. Dillon and E. R. Gaillard (2004) Observation of A2E oxidation products in human retinal lipofuscin. Exp. Eye Res. 78, 895898.
  • 317
    Radu, R. A., N. L. Mata, A. Bagla and G. H. Travis (2004) Light exposure stimulates formation of A2E oxiranes in a mouse model of Stargardt's macular degeneration. Proc. Natl. Acad. Sci. USA 101, 59285933.
  • 318
    Mainster, M. A., W. T. Ham and F. C. Delori (1983) Potential retinal hazards—instrument and environmental light sources. Ophthalmology 90, 927932.
  • 319
    Darrow, R. A., R. M. Darrow and D. T. Organisciak (1997) Biochemical characterization of cell specific enzymes in light-exposed rat retinas: oxidative loss of all-trans retinol dehydrogenase activity. Curr. Eye Res. 16, 144151.