The effect of fingomolid (FTY720) protecting the retina of rats from light-induced retinal degeneration (LIRD)

Abstract

Object: Fingomolid (FTY720), an immunosuppressive agent, was found to protect the retina against light stress in our previous study. In this study, we investigate whether FTY720 has a protective effect on retinal degeneration and whether immune response is involved in photoreceptor apoptosis in light-induced retinal degeneration (LIRD) in rats. Methods: Sprague-Dawley rats raised in cyclic dim light were exposed to 2700 lux white light for 6 hours to build LIRD animal models. FTY720 (10.0 mg/kg) or vehicle was administered intraperitoneally to rats 0.5 h before light exposure. Histology and F-ERGs analysis were used to evaluate the structure and function of retina, respectively. The apoptosis of retinal cells was detected by TUNEL assay. The immune T cells on light-damaged retina were measured by immunofluorescence analysis, and the expression of immune proteins was examined by western blot. Results: After light exposure, significant reductions in ERGs response were observed in vehicle-treated (VLD) group, whereas there was no significant difference between FTY720-treated (FTY-LD) group and normal group. A slight thinning was observed in FTY-LD group, which was not reflected in the full field ERG responses. Pretreatment with FTY720 inhibited light-induced photoreceptor apoptosis and protected retinal structure and function against light damage. CD3+ and CD8+ T molecules were increased in the VLD group, but did not occur on the whole retina in rats treated with FTY720. The expression of CD3+ and CD8+ proteins were up-regulated by light exposure and suppressed by FTY720 pretreatment. Light stress activated the microglial cells, and FTY720 could suppress the activation. Conclusion: FTY720 could inhibit apoptosis and suppress CD3+ and CD8+ T cells and microglial activation in light-damaged retina in rats, showing an obvious protective effect on photoreceptors. These results help to better understand the pathogenesis of LIRD, and FTY720 may provide therapeutic benefit for retinal diseases.