Diabetic retinopathy (DR) is a leading cause of vision loss among working-age adults and is characterized by progressive retinal microvascular dysfunction driven by hyperglycemia-induced inflammation and oxidative stress. Histone deacetylase 6 (HDAC6), a cytoplasmic deacetylase involved in multiple cellular processes, has been implicated in vascular pathology; however, its specific role in retinal endothelial cells remains unclear. In this study, we investigated whether endothelial-specific deletion of HDAC6 protects against diabetic retinal injury. Endothelial HDAC6 knockout mice were generated using VE-cadherin–Cre recombination and subjected to streptozotocin-induced diabetes. Retinal vascular integrity, inflammatory and oxidative stress responses, endothelial senescence, and visual function were assessed during the course of hyperglycemia. Diabetic control mice developed characteristic features of DR, including vascular dysfunction, heightened inflammatory and oxidative stress responses, increased endothelial senescence, and impaired visual function. In contrast, endothelial-specific HDAC6 deletion markedly attenuated these pathological changes, preserving retinal vascular integrity and visual performance while reducing oxidative stress and inflammation. These findings identify endothelial HDAC6 as a key contributor to diabetes-induced retinal vascular injury and suggest that targeting endothelial HDAC6 may represent a promising therapeutic strategy for preventing microvascular damage and vision loss in DR.

In recent years, the role of non-coding RNAs in human physiology and pathology has emerged as an essential avenue of investigation. Among others, studies identifying the biological role of microRNAs (miRNAs) have paved the way for future inquiries on the importance and biological significance of non-coding RNAs. In this review, we provide an overview of miRNAs’ biology and their contribution to the pathogenesis of diabetic retinopathy (DR). This complication of diabetes is the leading cause of blindness in adults, affecting more than 4 million people in the US alone and over 103 million people worldwide. Despite the tremendous efforts of the scientific community and the pharmaceutical industry, the development of new, more effective therapeutic and diagnostic tools for DR to date remains an unmet need. More than a decade from the initial work assessing miRNA expression profiles in diabetic patients, we have learned the impact of these signaling molecules in DR and garnered knowledge of their complexity and their potential as new diagnostic and therapeutic targets for this potentially blinding condition.