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

PURPOSE: Fingolimod (FTY720), an immunosuppressive agent, has previously shown protective effects against light-induced retinal injury in our prior work. In this study, we further explored whether 10 mg/kg FTY720 alleviates light-induced retinal degeneration (LIRD) in rats, and clarified its potential dual roles in suppressing retinal immune responses and inhibiting photoreceptor apoptosis during LIRD progression.

METHODS

Sprague-Dawley rats raised in cyclic dim light were exposed to 2700 lx white light for 6 h to establish LIRD animal models. FTY720 (10.0 mg/kg) or vehicle was administered intraperitoneally to rats 0.5 h before light exposure. Histology and F-ERG analyses were used to evaluate the structure and function of retina. TUNEL assay was performed to detect the apoptosis of retinal cells, and Immunofluorescence analysis was performed to evaluate both infiltrating T lymphocytes and activated microglia in light-damaged retinas.

RESULTS

After light exposure, significantly reduced F‑ERG a‑ and b‑wave amplitudes, massive photoreceptor loss and thinning of the outer nuclear layer were observed in the vehicle‑treated group (VLD). No obvious structural and functional abnormalities were detected in the FTY720‑treated group (FTY), whose indicators were comparable to those of the non‑light‑damaged group (NLD). Pretreatment with FTY720 reduced light‑induced photoreceptor apoptosis and protected retinal structure and function against light damage. The number of CD3⁺CD4⁺ and CD3⁺CD8⁺ T lymphocytes was markedly elevated in the VLD group, whereas retinal T‑cell infiltration was remarkably restricted in FTY720‑pretreated rats. Additionally, light exposure triggered microglial activation, proliferation and migration in the outer retina, which was effectively suppressed by FTY720 pretreatment.

CONCLUSION

FTY720 reduces photoreceptor apoptosis, decreases CD3⁺CD4⁺ and CD3⁺CD8⁺ T‑lymphocyte infiltration, and mitigates microglial activation in light‑injured rat retinas, conferring prominent photoreceptor‑protective effects. These findings deepen our understanding of the pathogenic mechanisms underlying LIRD and suggest that FTY720 may serve as a promising therapeutic agent for retinal degenerative disorders.