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

• Published in: Biochimica et biophysica acta. General subjects Vol. 1869; no. 7; p. 130814
• Main Authors: Savitikadi, Pandarinath, Dash, Lucky, Angadi, Kiran Kumar, Reddy, G. Bhanuprakash, Reddy, V. Sudhakar
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2025
• Subjects: alpha-Crystallin A Chain; alpha-Crystallin B Chain - administration & dosage; alpha-Crystallins - administration & dosage; Animals; apoptosis; Apoptosis - drug effects; caspase-3; Cataract; Cataract - drug therapy; Cataract - etiology; Cataract - metabolism; Cataract - pathology; Cataract - prevention & control; Diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes Mellitus, Experimental - pathology; Disease Progression; endoplasmic reticulum; Endoplasmic Reticulum Stress - drug effects; eye lens; hyperglycemia; Lens, Crystalline - drug effects; Lens, Crystalline - metabolism; Lens, Crystalline - pathology; Male; mammals; Mini peptide; oxidative stress; Oxidative Stress - drug effects; peptides; Peptides - administration & dosage; Peptides - pharmacology; Protein aggregation; protein content; Rats; Rats, Sprague-Dawley; Streptozocin; Streptozotocin; therapeutics; Α-Crystallin; Cataract; Protein aggregation; Diabetes; Α-Crystallin; Streptozotocin; Mini peptide
• ISSN: 0304-4165; 1872-8006; 1872-8006
• DOI: 10.1016/j.bbagen.2025.130814

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. •Systemic administration of mini α-crystallin peptides delay the diabetic cataract in rats.•Mini α-crystallin peptides reduce the formation of protein cross-links and high molecular weight aggregates in diabetic cataractous lens.•Mini α-crystallin peptides attenuate cellular stress (oxidative and endoplasmic reticulum stress)-induced by hyperglycemia.•Mini α-crystallin peptides protect the lens from hyperglycemia-induced apoptosis.