Metabolic Dysfunction and Inflammation in Diabetic Retinopathy: Insights From Metabolomics and Cytokine Analysis

Diabetic retinopathy (DR) is a leading vision-threatening disease and a common complication of diabetes. However, the understanding of how metabolic dysfunction correlates with ocular inflammation in DR remains poorly understood. Therefore, in this study, we investigated the association between these two factors in DR.

Using untargeted metabolomics analysis and mass spectrometry detection, the plasma metabolic characteristics of 27 DR patients (15 with nonproliferative diabetic retinopathy [NPDR] and 12 with proliferative diabetic retinopathy [PDR]) and 8 healthy controls (HCs) were examined. Additionally, the concentrations of inflammatory factors and vascular endothelial growth factor (VEGF) in their aqueous humor were measured. Further analysis was conducted to evaluate the correlation between metabolic disorders and abnormalities in inflammatory factors and VEGF in the aqueous humor.

Metabolomic analysis revealed significant metabolic dysregulation in DR, with PDR exhibiting particularly pronounced alterations compared to NPDR and HC. ROC analysis identified creatinine, glutamine, indoleacetic acid, and methionine as reliable biomarkers for distinguishing PDR. Elevated cytokines, such as IL-6, IL-8, and VEGF, were significantly correlated with specific metabolism pathways.

Our study highlights potential biomarkers for DR stratification and provide novel insights into the link between metabolic dysfunction and ocular inflammation/ischemia in PDR.