Protection Of Mouse Photoreceptors By BDNF In Retinal Light Damage

PURPOSE: To establish the mouse model of retinal photo-injury with intravitreal injection of brain-derived neurotrophic factor(BDNF) to investigate the protective effect of exogenous BDNF on retinal exposed to visible light. METHODS:120 mice were divided randomly into normal control group(I group), merely light damage group(II group) and experimental group(III group). In III group,the left eyes belong to III_BDNF group and the right eyes belong to III_PBS group. All mice were maintained under cyclic light environment for 7 days, and then were kept in darkness for 36 hours.II and III groups were exposed to constant fluorescent light (8894±398Lx) for 2 hours. All mice were killed at the following time points after light exposure,16hr,24hr,36hr,72hr,with the latter time intervals after exposure spent in darkness. The morphologic changes of the retina were observed by light and electron microscopes. Terminal deoxynucleotidyl transferase-mediated dUTP nick and labeling (TUNEL) technique was used to assess apoptosis. The thickness of the out nuclear layers and apoptosis index were measured with Image Analysis System. RESULT: 1. Histopathologic observation: The retina of I group was morphologically normal with distinct structural layers and regular arrangement of out and inner segment. No positive marked cell was found when we distinguished apoptotic cells by TUNEL method. Nuclear chromation had even electronic density. In II and III_PBS groups, the arrangement of outer and inner segment were disordered. The thickness of the out nuclear layers decreased. Many TUNEL-positive nuclei were observed only in the outer nuclear layer. At 36 hr, TUNEL-positive RPE nuclei were observed. In III_BDNF group, 10～12 rows of nuclei were still present, not only were more cell nuclei present ,but also the surviving photoreceptors had greater integrity,with no obvious damage to the RPE. The apical microvilli of RPE linked outer segments well. Only a part of mitochondria of the inner segment were swollen. 2. Measurement of mean ONL thickness: ONL of I group was the thickest. The longer after light exposure , the thinner ONL of II,III_PBS and III_BDNF groups presented. Apart that there was no statistical difference between 24hr and 36hr (P>0.05).there were significant difference among other time points(P<0.05).At 16hr,24hr,36hr,72 hr after light exposure, ONL of III_BDNF group was significant thicker than II ,III_PBS groups(P<0.05) . 3. Measurement of mean AI: AI of I group at each time point was 0. The peak of II and III_PBS occurred at 24hr. At 16hr, 24hr, 36hr, AI of III_BDNF group was significant lower than II and III_PBS groups(P<0.05),and the peak occurred at 36hr.There was no statistical difference among II ,III_PBS and III_BDNF groups at 72 hr(P>0.05). CONCLUSION: 1. Photoreceptors of mice can be significantly protected from the damaging effects of visible light by intravitreal injection of BDNF. The probable protective mechanism of BDNF is: ⑴,BDNF reduces photoreceptors apoptosis; ⑵,BDNF resists the free radicals and lipid peroxids. 2. Light-exposure might cause DNA-repair mechanisms.