Diabetic retinopathy (DR) is the leading cause of blindness among American working populations. Oxidative stress is one of the major culprits contributing to the pathogenesis of DR. In this study, we tested whether melatonin, a potent antioxidant, was able to alleviate DR complications in streptozotocin (STZ)-induced diabetic mice. Melatonin was given through oral gavage to imitate the most commonly used intake route in humans. Electroretinogram (ERG) recordings were used to measure retinal light responses, and fluorescein angiography (FA) was used to assess changes in retinal vasculature chronologically. Three months after STZ-induced diabetes, eyes were harvested and analyzed for molecular changes using immunofluorescent staining. Cultured 661W cells, a photoreceptor-derived cell line, were used to determine the effect of melatonin on high glucose (HG) treated 661W cells. There was no significant difference in the body weight among the control, STZ-diabetic, and melatonin treated STZ-diabetic mice, but melatonin treatments appeared to further increase systemic hyperglycemia. Melatonin treatments had a temporarily protective effect on dampened retinal light responses in the STZ-diabetic mice. However, melatonin treatments prevented STZ-induced changes in retinal vasculature, including venous beading and increased vessel length. Melatonin treatments also reversed the disturbed mitochondrial dynamics and altered mitochondrial calcium storage in STZ-diabetic retinas in vivo and HG-treated 661W cells in vitro. Thus, daily oral intake of melatonin might have a protective effect against diabetes-associated retinal microvascular complications.
