αA-Crystallin Attenuates Retinal Ischemia-Reperfusion Injury

Purpose To explore the protective effect and underlying mechanism of exogenous αA-crystallin (CRYAA), a molecular chaperone with antioxidant properties, in retinal ischemia-reperfusion (I/R) injury via modulation of the Nrf2/HO-1 signaling pathway.Methods In vivo, retinal I/R injury was induced in Sprague Dawley rats by transient intraocular pressure elevation, followed by intravitreal CRYAA administration. In vitro, human retinal microvascular endothelial cells (HRMECs) were exposed to H2O2-induced oxidative stress with or without CRYAA treatment. Oxidative markers (ROS, MDA, SOD), apoptosis (TUNEL, Caspase-3), and Nrf2/HO-1 pathway activation were evaluated via histopathology, biochemical assays, Western blotting, and flow cytometry. Nrf2 overexpression and siRNA knockdown were performed to validate pathway involvement.Results CRYAA attenuated retinal edema and structural disorganization in I/R rats, restore partial retinal blood flow, reduced ROS (p < 0.05) and MDA levels, restored SOD activity (p < 0.05), and suppressed apoptosis by downregulating Caspase-3 (p < 0.05). Mechanistically, CRYAA enhanced Nrf2 phosphorylation, nuclear translocation, and HO-1 expression (p < 0.05). Nrf2 overexpression amplified these effects, while Nrf2 silencing abolished CRYAA’s protection, confirming pathway dependency.Conclusions Exogenous CRYAA mitigates retinal I/R injury by activating the Nrf2/HO-1 axis, reducing oxidative stress, and inhibiting apoptosis. These findings highlight CRYAA’s therapeutic potential for ischemic retinal disorders and underscore Nrf2 as a critical mediator of its protective effects.