Aerobic Exercise Preserves Retinal Integrity in Type 2 Diabetic Zebrafish in Association With Skeletal Muscle Mitochondrial Homeostasis

Diabetic retinopathy is a major complication of type 2 diabetes mellitus (T2DM), yet effective early interventions that simultaneously address systemic metabolic dysfunction and retinal injury remain limited. Here, using a zebrafish model of T2DM under continued diabetic challenge, we show that aerobic exercise preserves retinal integrity in parallel with broad metabolic and mitochondrial adaptations. Aerobic exercise improved glucolipid metabolic status, attenuated skeletal muscle injury, restored mitochondrial ultrastructure, and increased ATP content and mitochondrial complex I and III activities. These changes were accompanied by reduced inflammatory and oxidative stress burden, reflected by lower IL-1β, IL-6, TNF-α, and MDA levels and higher CAT and SOD activities. Retinal injury was concurrently alleviated, as indicated by increased inner and outer nuclear layer thicknesses and reduced apoptosis, together with improvement in behavioral abnormalities. Correlation analyses further linked inflammatory and oxidative stress indices with mitochondrial energy metabolism-related indices and retinal structural measures. Collectively, these findings suggest that exercise-associated retinal protection occurs in parallel with improved systemic metabolic status and preservation of skeletal muscle mitochondrial homeostasis under diabetic conditions, highlighting aerobic exercise as a potential early strategy for limiting diabetes-associated retinal vulnerability.