Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage
Article first published online: 9 FEB 2012
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry
Journal of Neurochemistry
Volume 121, Issue 1, pages 146–156, April 2012
How to Cite
Okano, K., Maeda, A., Chen, Y., Chauhan, V., Tang, J., Palczewska, G., Sakai, T., Tsuneoka, H., Palczewski, K. and Maeda, T. (2012), Retinal cone and rod photoreceptor cells exhibit differential susceptibility to light-induced damage. Journal of Neurochemistry, 121: 146–156. doi: 10.1111/j.1471-4159.2012.07647.x
- Issue published online: 14 MAR 2012
- Article first published online: 9 FEB 2012
- Accepted manuscript online: 5 JAN 2012 09:55AM EST
- Received November 7, 2011; revised manuscript received December 23, 2011; accepted December 23, 2011.
- age-related macular degeneration;
- Stargardt’s disease;
- visual cycle
J. Neurochem. (2012) 121, 146–156.
All-trans-retinal and its condensation-products can cause retinal degeneration in a light-dependent manner and contribute to the pathogenesis of human macular diseases such as Stargardt’s disease and age-related macular degeneration. Although these toxic retinoid by-products originate from rod and cone photoreceptor cells, the contribution of each cell type to light-induced retinal degeneration is unknown. In this study, the primary objective was to learn whether rods or cones are more susceptible to light-induced, all-trans-retinal-mediated damage. Previously, we reported that mice lacking enzymes that clear all-trans-retinal from the retina, ATP-binding cassette transporter 4 and retinol dehydrogenase 8, manifested light-induced retinal dystrophy. We first examined early-stage age-related macular degeneration patients and found retinal degenerative changes in rod-rich rather than cone-rich regions of the macula. We then evaluated transgenic mice with rod-only and cone-like-only retinas in addition to progenies of such mice inbred with Rdh8−/−Abca4−/− mice. Of all these strains, Rdh8−/−Abca4−/−mice with a mixed rod–cone population showed the most severe retinal degeneration under regular cyclic light conditions. Intense light exposure induced acute retinal damage in Rdh8−/−Abca4−/− and rod-only mice but not cone-like-only mice. These findings suggest that progression of retinal degeneration in Rdh8−/−Abca4−/− mice is affected by differential vulnerability of rods and cones to light.