Methyglyoxal reshapes the transcriptional network of human retinal endothelial cells [RNA-seq]

A primary event of DR is the functional impairment of microvascular cells (i.e., pericytes and endothelial cells) and pathological changes in the retinal neurovascular unit. In diabetes-related complications, advanced glycation end products (AGEs) play a pivotal role in oxidative damage induced by chronic hyperglycemia particularly in damaging retinal endothelial cells.

Methylglyoxal (MGO) is the most reactive AGE precursor, able to induce vascular damage, neuroretinal dysfunction and retinal lesions. Here, we demonstrate that sublethal doses of MGO induce protein glycation adduct formation in human retinal endothelial cells (hRECs), impairing the migratory and tube-forming capabilities. Moreover, transcriptome and miRNome analyses highlighted extensive perturbations in gene expression and microRNA profiles, especially related to gene expression regulation, cell cycle, cell death and vasculature development.