Alpha-crystallins protect photoreceptors during retinal detachment through FAIM2 regulation

Abstract We evaluated the role of α-crystallin in photoreceptor survival in an experimental model of retinal detachment, and its association with Fas apoptosis inhibitory molecule 2 (FAIM2). Retina/RPE separation was induced in rat and mouse eyes by the subretinal injection of hyaluronic acid, 1%. Retinal tissues were analyzed for the presence αA-crystallin and αB-crystallin proteins using immunohistochemistry and immunoblot. Indices of photoreceptor death were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and cell counts. The 661W cells subjected to FasL were used as a cell model of photoreceptor degeneration to assess the mechanisms of the protective effect of αA-crystallin and its phosphorylation on T148. In addition to the associated cell-death, FAIM2 and αA-crystallin interaction were evaluated using co-immunoprecipitation assay. α-Crystallin protein levels were rapidly induced in response to retinal detachment, with αA-crystallin playing a particularly important role in protecting photoreceptors during retinal detachment. Our data also shows that FAIM2, an intrinsic neuroprotective protein in photoreceptors, interacts with α-crystallins following retinal detachment. Mechanistically, our work also demonstrated that the phosphorylation of αA-crystallin is essential for the interaction of αA-crystallin with FAIM2 and their neuroprotective effect. Thus, αA-crystallin is involved in the regulation of photoreceptor survival during retinal detachment, playing a key role in the stabilization of FAIM2, an important modulator of photoreceptor cell survival under chronic stress condition.