Melatonin ameliorates retinal neurovascular degeneration in Rd1 mice by inhibiting oxidativestress.

Oxidative stress has been involved in the occurrence of retinal photoreceptor degeneration and retinal vascular dysfunctions. This study investigated the effects of melatonin (MLT) on neurovascular changes in rd1 mice, evaluating its therapeutic potential as an antioxidant for retinal degeneration. MLT was administered to rd1 mice at postnatal day 7 (P7), and retinal vascular alterations were assessed using retina flatmounts, while neural and functional changes were evaluated through frozen sections and electroretinography at P14. In vitro, human retinal microvascular endothelial cells (HRMECs) were treated with MLT to counteract oxidative stress induced by H2O2. Analyses included assessments of cell function, apoptosis, oxidative stress, and inflammatory markers in both in vivo and in vitro models. The results demonstrated that MLT significantly improved retinal vascular densities in the deep and superficial layers at P14 and P21, though not fully restoring them to wild-type levels. Additionally, MLT exerted protective effects against photoreceptor degeneration, oxidative stress, and inflammation, partially preserving retinal function. In vitro, MLT alleviated functional abnormalities and reduced cell death in HRMECs by decreasing reactive oxygen species levels. These findings suggest that MLT holds promise as a therapeutic approach for retinal degeneration by mitigating oxidative stress, thereby protecting photoreceptors and retinal vasculature. This underscores the importance of vascular preservation in developing therapeutic strategies for retinal degenerative diseases.