Post-translational modifications in diabetic retinopathy: a comprehensive review of mechanisms, crosstalk and clinical prospects.

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes mellitus (DM) and remains the leading cause of blindness among the working-age population. Neurodegeneration, microvascular dysfunction, gliosis, and neovascularization are key hallmarks of DR. Emerging evidence has highlighted the involvement of protein post-translational modifications (PTMs) in DR progression. PTMs, including glycosylation, phosphorylation, ubiquitination, methylation, and acetylation, regulate protein stability, localization, and activity in response to hyperglycemic stress and oxidative damage, thereby perturbing the function of retinal vascular endothelial cells, neurons, and glial cells. A systematic literature search was performed in PubMed for studies published up to June 2025, using a combination of the term "Diabetic retinopathy" with keywords related to post-translational modifications, including "glycosylation", "phosphorylation", "ubiquitination", "methylation", "acetylation", and "SUMOylation". Eligible studies were limited to English-language publications that specifically examined the interaction between PTMs and DR, including both original research and review articles. Studies were excluded if they only mentioned PTMs and DR without investigating the direct relationship between them. This review did not involve formal statistical analysis or meta-analytic techniques. In this review, we first outlined the physiological roles of PTMs in vascular leakage, neovascularization, reactive gliosis, and retinal neuronal degeneration during DR. Next, we examined the contributions and interplay of distinct PTM types in these pathological events. Lastly, we explored the potential of PTMs as biomarkers and therapeutic targets in DR. A deeper understanding of the role of PTMs in DR may provide novel mechanistic insights and facilitate early diagnosis and treatment of DR.