COX17 Attenuates Diabetes-Associated Retinal Injury by Improving Mitochondrial Function

Area of Science:

• Ophthalmology
• Diabetology
• Mitochondrial Biology

Background:

• Diabetic retinopathy (DR) is a major cause of blindness globally.
• Cytochrome C oxidase copper chaperone (COX17) is crucial for mitochondrial function.
• COX17 overexpression has shown benefits in renal tissue mitochondrial function.

Purpose of the Study:

• To investigate the role of COX17 in diabetic retinopathy.
• To determine if COX17 alleviates DR by regulating mitochondrial function.

Main Methods:

• Streptozotocin (STZ)-induced diabetes in rats.
• Adeno-associated virus-mediated COX17 overexpression in rat vitreous.
• High-glucose (HG) culture of human retinal microvascular endothelial cells (HRMECs).
• Assays included immunofluorescence, enzymatic histochemistry, CCK-8, DCFH-DA, flow cytometry, western blot, and real-time PCR.

Main Results:

• COX17 expression was reduced in diabetic rat retinas and HG-stimulated HRMECs.
• COX17 overexpression improved retinal thickness and reduced neovascularization in diabetic rats.
• COX17 overexpression decreased reactive oxygen species (ROS) and apoptosis, while increasing Cytochrome C oxidase activity, mtDNA copy number, ATP content, and mitochondrial membrane potential (MMP) in both models.
• COX17 overexpression enhanced cell viability and reduced apoptosis in HG-induced HRMECs.

Conclusions:

• COX17 overexpression demonstrates protective effects in diabetic retinopathy.
• Stabilizing mitochondrial function is the key mechanism by which COX17 exerts its protective effects.
• COX17 holds potential as a therapeutic target for managing diabetic retinopathy.