Original Article Glial Cell–Derived Cytokines Attenuate the Breakdown of Vascular Integrity in Diabetic Retinopathy

The blood-retinal barrier (BRB) is a biological unit com-prised of specialized capillary endothelial cells firmly con-nected by intercellular tight junctions and endothelium-surrounding glial cells. The BRB is essential for maintaining the retinal microenvironment and low permeability and is compromised in an early phase during the progression of diabetic retinopathy. Here, we demonstrate that retinoic acid receptor (RAR) stimulants preferentially act on glial cells rather than endothelial cells, resulting in the en-hanced expression of glial cell line–derived neurotrophic factor (GDNF) through recruitment of the RAR-driven trans-acting coactivator to the 5-flanking region of the gene promoter. Conversely, RAR decreases expression of vascular endothelial growth factor (VEGF)/vascular per-meability factor. These gene expression alterations causall