αA-Crystallin Attenuates Retinal Ischemia-Reperfusion Injury.

Abstract

PURPOSE: To explore the protective effect and underlying mechanism of exogenous &#x3b1;A-crystallin (CRYAA), a molecular chaperone with antioxidant properties, in retinal ischemia-reperfusion (I/R) injurymodulation of the Nrf2/HO-1 signaling pathway. METHODS: , retinal I/R injury was induced in Sprague Dawley rats by transient intraocular pressure elevation, followed by intravitreal CRYAA administration., human retinal microvascular endothelial cells (HRMECs) were exposed to HO-induced oxidative stress with or without CRYAA treatment. Oxidative markers (ROS, MDA, SOD), apoptosis (TUNEL, Caspase-3), and Nrf2/HO-1 pathway activation were evaluatedhistopathology, 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 (&#x2009;<&#x2009;0.05) and MDA levels, restored SOD activity (&#x2009;<&#x2009;0.05), and suppressed apoptosis by downregulating Caspase-3 (&#x2009;<&#x2009;0.05). Mechanistically, CRYAA enhanced Nrf2 phosphorylation, nuclear translocation, and HO-1 expression (&#x2009;<&#x2009;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.