Diabetic retinopathy (DR) remains a leading cause of preventable vision impairment among working-age adults, but the molecular mechanisms contributing to disease progression remain incompletely understood. A study published in Nutrition and Metabolism evaluated macrophage-associated proteomic changes and the relationship between circulating vitamin C levels and DR risk.

The analysis included quantitative proteomics and bioinformatics evaluation of peripheral blood macrophages from patients with proliferative DR, non-proliferative DR, diabetes without retinopathy, and non-diabetic controls. Additional experiments used THP-1 cells exposed to sustained hyperglycemia and retinal lysates from streptozotocin-induced mice to assess TPT1 expression, autophagy-related mediators, and reactive oxygen species production. Two-sample Mendelian randomization analysis was performed to evaluate associations between circulating vitamin C levels and DR risk.

Findings

• Quantitative proteomics identified 265 proteins with significantly altered abundance in proliferative DR compared with controls, including 145 upregulated and 120 downregulated proteins.
• TPT1 emerged as a central hub within the macrophage protein interactome.
• TPT1 expression was markedly reduced under hyperglycemic conditions in THP-1 cells and retinal lysates from streptozotocin-induced mice.
• Reduced TPT1 expression was accompanied by impaired autophagic activity and increased reactive oxygen species production.
• Mendelian randomization analysis demonstrated an inverse association between circulating vitamin C levels and DR risk (OR, 0.09; 95% CI, 0.01–0.57; p=0.01).

The findings suggest that reduced TPT1 expression and impaired macrophage autophagy may contribute to DR progression, while circulating vitamin C levels demonstrated an inverse association with DR risk.