Clin Exp Pharmacol Physiol. 2026 Jan;53(1):e70098. doi: 10.1111/1440-1681.70098.
ABSTRACT
PURPOSE: Diabetic retinopathy (DR), a common complication of diabetes, is a leading cause of blindness globally. Cytochrome C oxidase copper chaperone (COX17) is important for Cytochrome C oxidase assembly, and COX17 overexpression is reported to improve mitochondrial function in renal tissue. This study aimed to explore whether COX17 alleviated DR by regulating mitochondrial function.
METHODS: Diabetes was induced in rats by a single intraperitoneal injection of 65 mg/kg streptozotocin (STZ). Overexpression of COX17 was performed by infection of adeno-associated virus into the vitreous body of rats 2 weeks after STZ injection. Human retinal microvascular endothelial cells (HRMECs) were cultured with high-glucose (HG) medium (20 mM d-glucose). Immunofluorescence assay, enzymatic histochemistry assay, CCK-8 assay, DCFH-DA staining, flow cytometry, western blot, and real-time PCR were performed.
RESULTS: COX17 expression was decreased in the retinal tissues of diabetic rats and HG-stimulated HRMECs. COX17 overexpression alleviated retinal neovascularisation and increased retinal thickness in diabetic rats. COX17 overexpression decreased ROS and apoptosis and increased Cytochrome C oxidase activity, mtDNA copy number, ATP content, and mitochondrial membrane potential (MMP) in both the retinal tissues of diabetic rats and HG-induced HRMECs. Overexpression of COX17 effectively reduced cell apoptosis and increased cell viability. Overexpression of COX17 increased mtDNA in HG-induced HRMECs.
CONCLUSIONS: Overall, our study suggested that COX17 overexpression exerted protective effects in the retinas of diabetic rats and in HRMECs by stabilising mitochondrial function.
PMID:41347662 | DOI:10.1111/1440-1681.70098