Systemically administered mini α-crystallin peptide delays cataract progression in streptozotocin-induced diabetic...

α-Crystallin in the mammalian eye lens composed of αA-Crystallin (αAC) and αB-Crystallin (αBC) subunits present in a 3:1 ratio. These proteins exhibit chaperone-like activity, helping to protect cells from various forms of stress. Specific sequences within αAC (⁷⁰KFVIFLDVKHFSPEDLTVK⁸⁸) and αBC (⁷³DRFSVNLDVKHFSPEELKVK⁹²) have been shown to possess effective chaperone and anti-apoptotic properties. However, their protective effects in diabetic cataract (DC) have not been explored. The current study explored the protective effects of systemically administered mini-αA and αBC peptides, both individually and in combination (3:1 ratio) against streptozotocin (STZ)-induced DC in rats. Hyperglycemia was induced in Sprague-Dawley rats through intraperitoneal (I.P.) injection of STZ, while control rats received PBS. Starting from the onset of cataract development, a group of diabetic rats was treated with mini-αA, or mini-αB, or their combination for four months via IP administration. Cataract progression and maturation were monitored using a slit lamp biomicroscope. To understand the underlying biochemical and molecular processes, we assessed changes in protein content, protein insolubilization, oxidative stress, endoplasmic reticulum (ER) stress, apoptotic cell death, and caspase-3 activity. Although the mini peptides did not prevent STZ-induced hyperglycemia, they delayed cataract progression in diabetic rats. Furthermore, mini peptides reduced protein aggregation and insolubilization, alleviated oxidative and ER stress, and mitigated hyperglycemia-induced apoptosis by lowering caspase-3 activity and Bax levels. This study demonstrates that systemic administration of mini α-crystallin peptides can delay DC progression by mitigating protein aggregation, oxidative stress, ER stress, and apoptosis. These findings suggest potential therapeutic applications for mini α-crystallin peptides in treating DC.