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Keywords:

  • brain-derived neurotrophic factor;
  • electroretinogram;
  • neuroprotection;
  • neurotrophins;
  • photoreceptor;
  • retinal damage

Abstract

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

We investigated the neuroprotective effects of brain-derived neurotrophic factor (BDNF) and its influence on the functional recovery of the retina following light-induced retinal damage by electroretinogram (ERG). Rats were exposed to constant fluorescent light for 2, 5, 7, or 14 days, then returned to a cyclic light environment for 14 days. The result indicated that BDNF had few effects on the a-wave amplitude, but there was a statistically significant difference in the b-wave amplitudes between BDNF-treated and control eyes from day 0–14 of the recovery period following 2 days of light exposure (p < 0.05). Our findings suggest that BDNF not only protects the retinal neuronal function but also enhances the recovery from retinal light damage.

Abbreviations used
AMD

aged-macular degeneration

BDNF

brain-derived neurotrophic factor

CNTF

ciliary neurotrophic factor

ERG

electroretinogram

GDNF

glia cell line-derived neurotrophic factor

GFAP

glial fibrillary acidic protein

INL

inner nuclear layer

mEPSCs

miniature EPSCs

NGF

nerve growth factor

NT-3

neurotrophin-3

ONH

optic nerve head

ONL

outer nuclear layer

pERK

phosphorylated extracellular signal-regulated kinase

RP

retinitis pigmentosa

Brain-derived neurotrophic factor (BDNF) is a member of a neurotrophin family that also includes nerve growth factor (NGF), neurotrophin-3 (NT-3), and NT-4/5. Neurotrophins have a potent ability to retard neuronal cell death and/or stimulate neuronal survival, regeneration, and neuron-related enzyme synthesis. BDNF is a potent and effective trophic factor for various neurons of the peripheral and central nervous systems (Lindsay et al. 1994; Yuen and Mobley 1996; Mattson et al. 2003), and it is expected to have therapeutic potential for the treatment of retinal diseases as well as disorders of the central nervous system (Ko et al. 2000).

BDNF and its high-affinity receptor, TrkB, are present in developing and adult retinas (Perez and Caminos 1995; Cellerino and Kohler 1997). We previously showed that BDNF has a neuroprotective effect on the retina against KCN-induced chemical ischaemia and glutamate toxicity (Ikeda et al. 1999; Kido et al. 2000). BDNF has also been shown to support cell survival and to enhance the axonal regeneration of axotomized retinal ganglion cells (Mey and Thanos 1993; Mansour-Robaey et al. 1994; Weibel et al. 1995; Peinado-Ramon et al. 1996; Sawai et al. 1996; Klocker et al. 1998).

Retinal damage in albino rodents caused by constant light exposure has been studied extensively. This is considered to be a useful animal model for retinitis pigmentosa (RP) and aged-macular degeneration (AMD) because, as in these disorders, a selective loss of photoreceptors is observed (Lisman and Fain 1995; Wu et al. 1996; Grimm et al. 2000). The cell death in this injury occurs by typical TUNEL-positive apoptosis (Chen et al. 1996; Joseph and Li 1996; Lansel et al. 1998; Organisciak et al. 1998).

The neuroprotective effects of neurotrophic factors on photoreceptors have been well studied by morphological analyses (LaVail et al. 1992). Recently, glia cell line-derived neurotrophic factor (GDNF) (Frasson et al. 1999; McGee et al. 2001) and ciliary neurotrophic factor (CNTF) were shown to exert functional protection against the degeneration of photoreceptors (LaVail et al. 1998). However, little is known about the effects of BDNF on the function of retinas. Here, we studied the efficacy of BDNF in protecting the retinal electroretinogram (ERG) response against constant light damage and influencing the recovery of the ERG response from light damage.

Animals and materials

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

Adult male Wistar rats (7 weeks old, Charles River, Yokohama, Japan) were used. All animal experiments were conducted according to the Guidelines of Experimental Animal Care issued by the Japanese Prime Minister's office. Regeneron Pharmaceutical Inc. (Tarrytown, NY, USA) supplied the recombinant methionine-free human BDNF.

Constant light exposure and BDNF administration

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

Male Wistar rats were obtained at 250–300 g (Charles River) and maintained in a cyclic light environment (12 h : 12 h, light : dark) for 7 or more days before the experiments. We examined five rats for each treatment group. Rats with vitreous opacity following the injection with vehicle or regent were omitted from the experiment.

Rats were then placed under constant fluorescent light at a luminance of approximately 150–200 foot candela (ft-c) for 2, 5, 7, and 14 days. One microgram of sterilized BDNF (1 μg/μL) was intravitreally injected into the rat eyeballs 2 days before the constant light exposure. The injection was performed with a 33-G needle, according to the method previously described (Faktorovich et al. 1992). One eye (left) of each rat was intravitreally injected with BDNF, and the other (right) with phosphate-buffered saline (PBS). The distribution of injected BDNF has been reported (Ikeda et al. 1999). After the constant light exposure, the rats were returned to the cyclic light condition (12 h : 12 h, light : dark) for a recovery period of 14 days.

Electroretinogram measurement

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

All rats were dark adapted for 4 h, and anaesthetized by intramuscular injection of a ketamine-xylazine mixture (50 mg, 7.1 mg/kg, respectively). ERG analysis was performed in a completely darkened room. The ERG was recorded with a MAC Laboratory/4S system (ADInstruments Ltd, Chalgrove, Oxfordshire, UK) connected to a digital oscilloscope (VC-11, Nihon Kohden). The ERG was recorded by white light flash stimulation with a Flash stimulator (SLS-3100, Nihon Kohden). The distance from the flash unit to the eye was 30 cm and the flash energy was 20 J. Data were analyzed with Scope, version 3.5/s (ADInstruments).

Morphological analysis of the retina

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

Rats were placed the constant light environment for 5 days, then killed under anaesthetization with ether. The eyeballs were immediately removed and fixed in a solution of 2.5% formalin-1% glutaraldehyde in PBS. Samples were embedded in Thechnovit 7100 (Heraeus Kulzer, Hanau, Belgium) and sectioned at a 2-μm thickness. The sections containing the optic nerve head (ONH) were stained with 0.1% cresyl violet for 1 min (Nissl staining) and observed under the microscope. Photomicrographs were taken of the posterior portions of the retina (100 μm each) lying 880, 1320, and 1760 μm away from the ONH in the superior and inferior regions.

Data analysis and statistics

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

In Table 1, data are presented as mean ± SEM of six to eight animals per each group. Data were evaluated by Student's t-test; *p < 0.05, **p < 0.01. In tables 2 and 3, data were presented as mean ± SEM of three to five animals per each group. Data were evaluated by variance followed by anova. In Fig. 3, statistical analysis was performed using Student's t-test. *p < 0.05, **p < 0.01.

Table 1.  Measurements of ONL thickness
Distance from ONH (μm)8808801320132017601760
SuperiorInferiorSuperiorInferiorSuperiorInferior
  1. Values are the mean ± SEM (n = 6–8) of the thickness of ONL for each treated group. ONH, optic nerve head. There is statically significant difference of ONL thickness between PBS- and BDNF-treated rats with constant light exposure. Statistical analysis was performed using Student's t-test (*p < 0.05, **p < 0.01).

Cyclic light + PBS33.9 ± 1.134.7 ± 1.331.1 ± 1.634.4 ± 1.133.1 ± 1.331.2 ± 1.5
Constant light + PBS14.6 ± 1.213.1 ± 1.79.9 ± 1.413.9 ± 2.111.0 ± 1.514.9 ± 2.2
Constant light + BDNF17.7 ± 1.520.7 ± 1.8*15.6 ± 1.0**20.9 ± 2.0*17.6 ± 1.4**22.2 ± 2.1*
Table 2.  Amplitude of ERG (a-wave)
Period of light exposure (days)Control2255771414
PBSBDNFPBSBDNFPBSBDNFPBSBDNF
Rec. days
0 day280.4 ± 24.574.6 ± 7.878.6 ± 7.849.6 ± 11.037.8 ± 6.072.7 ± 6.927.4 ± 4.853.9 ± 8.840.6 ± 13.9
2 days275.9 ± 15.4111.6 ± 18.4104.5 ± 19.946.8 ± 11.835.9 ± 11.530.5 ± 9.426.4 ± 2.028.0 ± 4.736.4 ± 14.6
5 days294.7 ± 10.4130.4 ± 40.5138.0 ± 37.580.3 ± 18.554.9 ± 26.443.9 ± 4.421.8 ± 7.721.0 ± 4.720.0 ± 4.5
7 days269.9 ± 16.8149.6 ± 39.5155.9 ± 32.564.7 ± 24.068.7 ± 24.542.8 ± 10.436.6 ± 4.914.4 ± 5.022.4 ± 3.1
10 days268.0 ± 9.5164.9 ± 49.5159.4 ± 33.553.6 ± 32.161.7 ± 28.941.4 ± 6.835.9 ± 11.214.2 ± 7.031.0 ± 1.8
14 days249.7 ± 3.7152.6 ± 38.0179.2 ± 32.476.3 ± 34.570.1 ± 25.032.9 ± 8.157.1 ± 7.723.2 ± 3.714.3 ± 1.3
Table 3.  Amplitude of ERG (b-wave)
Period of light exposure (days)Control2255771414
PBSBDNFPBSBDNFPBSBDNFPBSBDNF
  1. Tables 2 and 3 show the a- and b-wave amplitude, respectively, of light-exposed rats. Values are the mean ± SEM ( n  = 3–5) of the amplitude for each treated group. Rec. days, number of days the rats were in a cyclic light environment following the constant light exposure. There is no statically significant difference of a- and b-wave amplitude between PBS- and BDNF-treated rats. anova ( p  > 0.05).

Rec. days
0 day744.0 ± 71.7410.2 ± 62.2491.1 ± 52.2133.5 ± 36.0187.5 ± 37.482.3 ± 5.795.5 ± 15.9102.9 ± 12.061.7 ± 11.3
2 days781.6 ± 16.2358.3 ± 64.0446.3 ± 58.9139.0 ± 48.0199.3 ± 64.248.3 ± 8.1138.2 ± 33.854.8 ± 12.366.5 ± 9.5
5 days788.5 ± 55.4390.4 ± 122.8569.3 ± 125.2249.0 ± 95.4263.6 ± 83.9109.8 ± 31.8190.5 ± 48.460.3 ± 18.285.7 ± 9.9
7 days733.8 ± 38.8457.1 ± 128.0583.3 ± 69.6225.7 ± 77.3258.9 ± 75.8134.0 ± 35.5213.6 ± 46.652.7 ± 8.6109.9 ± 14.9
10 days788.5 ± 15.0498.6 ± 118.9636.8 ± 83.1261.5 ± 89.8307.0 ± 90.9158.1 ± 57.4273.1 ± 35.755.1 ± 16.799.6 ± 28.2
14 days706.9 ± 14.1466.4 ± 83.2712.5 ± 92.2279.1 ± 99.6343.9 ± 76.8214.3 ± 51.1320.0 ± 12.361.5 ± 25.9118.3 ± 39.2

Results

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

The ERG responses in the control (saline-injected) and BDNF-injected eyes of rats that had been exposed to 2, 5, 7, or 14 days of constant light were repeatedly measured, on day 0, 2, 5, 7, and 14 of the recovery period. All the ERG amplitudes of the a- and b-waves are summarized in Tables 2 and 3, respectively.

Effect of light damage on the ERG response and its recovery in control eyes

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

We first analyzed the natural recovery of the a- and b-wave amplitudes from various degrees of severity of light damage. As shown in Table 2, the a-wave amplitude of PBS-treated eyes was markedly reduced by 2 days of constant light exposure and partially recovered during the recovery period. However, there was no recovery in the cases with more than 5 days constant light exposure.

In contrast, the b-wave response was slightly more resistant to light exposure than the a-wave response: the b-wave amplitude retained more than 50% of the normal level immediately after 2 days of light exposure (Table 3). Moreover, the b-wave amplitude in the PBS-treated eyes was recovered to some extent, even in the cases with 5 and 7 days of light exposure (Table 3).

Protective effects of BDNF against light damage

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

The efficacy of BDNF in protecting the retina against light damage was first investigated by morphological analysis. Two days after intravitreal injection of BDNF, the rats were exposed to constant fluorescent light for 5 days. Figure 1(a and b) show that compared with normal rat eyes, the thickness of the photoreceptor layer of the PBS-treated with constant light for 5 days was reduced prominently. In contrast, the BDNF-treated eyes showed a much smaller reduction of the photoreceptor layer (Fig. 1c). In superior and inferior retina exposed with constant light for 5 days, the thickness of ONL was about 30–50% of the cyclic light conditioned retina. However, with the treatment of BDNF, the thickness of ONL was 40–70% of the control. These results coincide with the protective effects of BDNF reported previously (LaVail et al. 1992).

image

Figure 1. Photomicrographs of rat superior retina after exposure to constant light. ONL, outer nuclear layer. (a)  Control eye in the cyclic light environment. (b)  PBS-treated eye after 5 days of constant fluorescent light exposure. (c)  BDNF-treated eye after 5 days of constant fluorescent light exposure. BDNF protected the outer nuclear layer cells against injury due to the constant light. Scale bar, 50 μm.

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Next, the effects of BDNF on the a- and b-wave amplitudes were evaluated. Before these experiments, we investigated the influence of BDNF on the ERG pattern in naïve rats. It showed that there is no change in these patterns 2 days after the vitreous injection of BDNF (data not shown).

Figure 2 shows the typical ERG patterns obtained for rats undergoing each treatment. BDNF-treated eyes showed a recovery of retinal neuronal function, especially in the b-wave amplitude. The averages of the a-wave amplitudes in the PBS- and BDNF-treated eyes are shown in Table 2 . These data suggest that BDNF had no neuroprotective effect on the a-wave amplitudes (recovery day 0) nor did it influence the recovery from the damage (recovery day 2, 5, 7, 10, and 14).

image

Figure 2. Typical ERG pattern for rats after 2 days of light exposure. (a)  Pattern for an untreated rat kept in the cyclic light environment [12 h: light (< 500 lux), 12 h: dark]. (b and c) Patterns for PBS- and BDNF-treated rats, respectively, after they were exposed to a constant light environment for 2 days. The number of days indicates the recovery period (0, 2, 5, or 10 days) after 2 days of constant light exposure.

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Figure 2(a ) shows the pattern for an untreated rat kept in the cyclic light environment [12 h: light (< 500 lux), 12 h: dark]. Figure 2(b and c) show the patterns for PBS- and BDNF-treated rats, respectively, after they were exposed to a constant light environment for 2 days. The number of days indicates the recovery period (0, 2, 5, or 10 days) after 2 days of constant light exposure.

To eliminate the individual differences of the rats, we calculated the differences in the a-wave amplitude between the PBS-treated eye (left eye) and the BDNF-treated eye (right eye) for each animal (Fig. 3a). BDNF showed little effect on the a-wave amplitude on any recovery day after light damage except for an improvement on recovery day 14 after 2 days of light exposure.

image

Figure 3. Effect of BDNF on the amplitude of the a - (a) and b - (b) waves during the recovery period following 2 days of constant light exposure. Values are the means ± SEM ( n  = 3–5) of the differences between the ERG amplitude of BDNF-treated (left) and PBS-treated (right) eyes in individual rats. Statistical analysis was performed using Student's t -test. * p  < 0.05, ** p  < 0.01.

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In contrast to the a-wave amplitude, the b-wave amplitudes in the BDNF-treated eyes tended to be larger than those in the PBS-treated eyes following all durations of light exposure, especially in the case with 2 days of light exposure (Table 3). On recovery day 0, the b-wave amplitude of the BDNF-treated eyes was 80 μV higher than that of the PBS-treated eyes (p < 0.05), demonstrating the protective activity of BDNF (Fig. 3b) on inner nuclear layer (INL) cells. But this protection of the retina by BDNF was not observed by the morphological analyses, because damage on INL was not detected by the morphological analyses observation. The b-wave amplitude was almost restored to the normal level in the BDNF-treated eyes on recovery day 14 after 2 days of light exposure. The effects of BDNF were not statistically significant when the average values of the amplitudes between the control and BDNF-treated groups were compared (Table 3). However, the analysis of the differences in the amplitudes between the PBS-treated and BDNF-treated eyes in individual rats clearly showed the efficacy of the BDNF treatment in rats receiving 2 days of light exposure. Furthermore, BDNF also improved the recovery of the b-wave responses (recovery days 2–14) (Fig. 3b). These findings suggest that BDNF not only protects the retinal function but also enhances the recovery of the retina from light damage. However, BDNF did not show this efficacy in cases where the rats had received more than 5 days of light exposure (data not shown).

Discussion

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References

In this study, the efficacy of BDNF in protecting retinal function against constant light damage and aiding its recovery from the damage was investigated by ERG analyses. Two components of the ERG were assessed: the negative a-wave potential, which is generated by the hyperpolarization of glutamatergic photoreceptors in response to light, and the positive b-wave potential, which reflects the depolarization of glutamatergic ON-bipolar cells in a secondary response to photoreceptor activation (Green and Kapousta-Bruneau 1999).

In this study, the protection and improved recovery from light damage by BDNF were clearly observed in the retinas of rats that had been exposed to 2 days of light, and the recovery of b-wave components was more obvious than that of a-wave components in the BDNF-treated eyes.

Organisciak et al. (1985 ) reported that the recovery of a-wave amplitude from light damage is correlated with the up-regulation of rhodopsin expression. Therefore, we investigated the effect of BDNF on the expression of rhodopsin in naïve rats. However, the intravitreal injection of BDNF did not change the expression levels of rhodopsin 2 days later (data not shown). This finding agrees with previous reports that the BDNF receptor, TrkB, is absent in photoreceptors ( Perez et al. 1995 ; Cellerino et al. 1997 ) and our result that BDNF showed few effects on the a-wave amplitude.

We observed a small effect of BDNF on the a-wave amplitude in rats on recovery day 14 after 2 days of light exposure (Fig. 3a). As discussed above, BDNF is not likely to act directly on photoreceptors because of the absence of its receptors on these cells (Perez et al. 1995; Cellerino et al. 1997). It is possible that BDNF supports photoreceptors indirectly, via the activation of Muller cells and other inner nuclear cells, which are secondary neurons in the retinal system and express TrkB receptor (Perez et al. 1995; Cellerino et al. 1997), because BDNF enhances the expression of glial fibrillary acidic protein (GFAP), phosphorylated extracellular signal-regulated kinase (pERK), and c-fos in these inner nuclear cells in vivo and in explant cultures (Wahlin et al. 2000). Our results are consistent with the hypothesis that BDNF elicits some effects on photoreceptors by acting indirectly through the activation of Muller cells and other retinal cells.

Constant light exposure causes primary damage of the outer nuclear cells but does not directly damage the inner nuclear cells. It has been reported that the b-wave amplitude is generated from the activation of AMPA receptors on rod-dependent bipolar cells or Muller cells in which TrkB is expressed. Recently, BDNF was found to affect AMPA receptor-mediated miniature EPSCs (mEPSCs) recorded from the CA1 pyramidal neurons in hippocampal slices (Lessmann et al. 1994; Tyler and Pozzo-Miller 2001). However, in these cells, BDNF increases the frequency but not the amplitude of the AMPA receptor-mediated miniature EPSCs. It is not certain that the contribution of AMPA receptors to the up-regulation of the b-wave amplitude may be large, but it cannot be denied that BDNF increases the amplitude of b wave via the AMPA receptor in the retinal system because higher frequency may cause higher amplitude of bipolar cells. Rather, the recovery of a- and b-wave amplitude by the injection of BDNF might be explained by an increase in glutamate release. BDNF rapidly and transiently enhances the depolarization-evoked release of glutamate in rat cortical neurons (Sala et al. 1998). It has been also reported that glutamate release is enhanced by BDNF in rat cerebellar granule cells (Numakawa et al. 1999). TrkB receptors are expressed in bipolar cells and Muller cells (Cellerino et al. 1997), which are important for b-wave occurrence. Therefore, it is very likely that BDNF improves the functions of the retina by stimulating glutamate release from Muller cells and bipolar cells. As previously reported, it has been shown that the deprivation of Glu decreases b-wave amplitude. In contrast, blocker for glutamate transporter maintained the b-wave occurrence in the isolated rat retina (Winkler et al. 1999). So, BDNF might stimulate glutamate release from Muller cells and bipolar cells via TrkB receptor and then glutamate enhance the b-wave amplitude via glutamate receptor on Muller cells and bipolar cells in the manner of paracrine or autocrine. However, in our previous report, we observed that BDNF attenuated the elevation of glutamate levels and protected retinal cells in a dose-dependent manner against potassium cyanide (KCN)-induced retinal damage (Ikeda et al. 1999). This discrepancy may reflect the two distinct aspects of BDNF action: the neuroprotective (Ikeda et al. 1999) and functional modulatory effects (Tyler et al. 2002).

Recently, it was demonstrated that the b-wave response of the ERG completely disappears in TrkB knockout mice, although the inner nuclear cells appear immunohistochemically and anatomically normal. This suggests that TrkB activation must be necessary for the functional neuronal network on which the generation of b-waves in the retina depends (Rohrer et al. 1999).

In this paper, the protective activity of BDNF for the retinal ERG response against constant light damage and the influence of BDNF on the recovery from light exposure were investigated. BDNF did not show any effect on the a-wave amplitude after light damage. In contrast, BDNF-treated eyes showed a significantly higher b-wave amplitude through the recovery period from day 0–14 following 2 days of light exposure. These data suggest that BDNF not only protects retinal neuronal function but also enhances the recovery from retinal light damage. As CNTF, fibroblast growth factor (FGF), and GDNF are well known to have direct effects on photoreceptors (Frasson et al. 1999; McGee et al. 2001; LaVail et al. 1998), the combination of BDNF with these factors might have a synergistic effect against retinal damage, which might be exploited to provide a more effective treatment for RP and AMD.

References

  1. Top of page
  2. Abstract
  3. Materials and methods
  4. Animals and materials
  5. Constant light exposure and BDNF administration
  6. Electroretinogram measurement
  7. Morphological analysis of the retina
  8. Data analysis and statistics
  9. Results
  10. Effect of light damage on the ERG response and its recovery in control eyes
  11. Protective effects of BDNF against light damage
  12. Discussion
  13. Acknowledgements
  14. References
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  • Frasson M., Picaud S., Leveillard T., Simonutti M., Mohand-Said S., Dreyfus H., Hicks D. and Sabel J. (1999) Glial cell line-derived neurotrophic factor induces histologic and functional protection of rod photoreceptors in the rd/rd mouse. Invest. Ophthalmol. Vis. Sci. 40, 27242734.
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