Activated microglia-induced neuroinflammatory cytokines lead to photoreceptor apoptosis in age-related macular degeneration-like mice model

Abstract

Background: Age-related macular degeneration (AMD) is mainly characterized by progressive deposits of drusen and photoreceptor apoptosis. Due to amyloid β (Aβ) is the main component of drusen, there is a great possibility that Aβ-induced activated microglia leads to inflammation, and plays a critical role in the pathogenesis of AMD. However, the relationship between activated microglia-mediated neuroinflammatory cytokines and photoreceptor apoptosis still remains unclarified.Results: In this study, we demonstrated that subretinal injection of Aβ1-42 induced the microglia activation and increased inflammatory cytokines, gave rise to photoreceptor apoptosis in mice. Our results were verified in vitro by co-culture of Aβ1-42 activated primary microglia and photoreceptor cell line 661W, and we also performed that p38 MAPK signaling pathway was involved in Aβ1-42 induced microglia activation and inflammatory cytokines release.Conclusions: Overall, our findings indicated that activated microglia-mediated neuroinflammatory cytokines contributed to photoreceptor apoptosis under the stimulation of Aβ1-42. Moreover, this study will provide a potential preventive and therapeutic approach for AMD treatment.