Idebenone Attenuates Diabetic Retinopathy by Modulating Autophagy Via Targeting Akt Signaling.

Abstract

Introduction: Diabetic Retinopathy (DR) is a common microvascular issue caused by diabetes. Idebenone (IDE) is a coenzyme Q10 analog and antioxidant that has been utilized in the treatment of neurodegenerative diseases.

Method: Our goal was to investigate how IDE might treat diabetic retinopathy. An in vivo DR model was established by injecting a single dose of streptozotocin (STZ). Rats were treated with IDE, and their vascular function was measured by ultrasound. The retina structure was checked by haematoxylin and eosin (HE) staining. The expression of biomarkers of autophagy and apoptosis was measured by western blotting assay. The retina endothelial cell line RF/6A was stimulated with high glucose (HG) and treated with IDE. Cell proliferation and apoptosis were assessed using the Edu assay, TUNEL assay, and flow cytometry, respectively.

Result: Reduced peak systolic velocity (PSV), mean velocity (MV), end-diastolic velocity (EDV), and increased pulsatility index (PI) and resistance index (RI) were observed in diabetic rats; however, these traits were reversed by IDE therapy. IDE alleviated the STZ-induced disordered retina structure. The IDE administration suppressed DR-induced apoptosis and autophagy both in vivo and in vitro. IDE suppressed the activation of Phosphatidylinositol 3 kinase (PI3K) signaling. Activation of PI3K abolished the IDE-alleviated retina damage and cell death.

Conclusion: IDE regulated the autophagy of retina cells to alleviate diabetic retinopathy via regulating the PI3K signaling pathway.