Airborne fine particulate matter (PM2.5) damages the inner blood–retinal barrier by inducing inflammation and ferroptosis in retinal vascular endothelial cells

This study was the first to explore the effect of airborne fine particulate matter (PM2.5) exposure on the inner blood–retinal barrier (iBRB). In this study, retinal vascular permeability and diameter were enhanced in the PM2.5-exposed animal model (1 mg/mL PM2.5, 10 μL per eye, 4 times per day, 3 days), together with observable retinal edema and increased inflammation level in retina. PM2.5-induced cell damage in human retinal microvascular endothelial cells (HRMECs) occurred in a time- and dose-dependent manner. Decreased cell viability, proliferation, migration, and angiogenesis, as well as increased apoptosis and inflammation, were observed. Iron overload and excessive lipid oxidation were also discovered after PM2.5 exposure (25, 50, and 100 μg/mL PM2.5 for 24 h), along with significantly altered expression of ferroptosis-related genes, such as prostaglandin-endoperoxide synthase 2, glutathione peroxidase 4, and ferritin heavy chain 1. Moreover, Ferrostatin-1, an inhibitor of ferroptosis, evidently alleviated the PM2.5-induced cytotoxicity of HRMECs. The present study investigated the in vivo effects of PM2.5 on retinas, revealing that PM2.5 exposure induced retinal inflammation, vascular dilatation, and caused damage to the iBRB. The crucial role of ferroptosis was discovered during PM2.5-induced HRMEC cytotoxicity and dysfunction, indicating a potential precautionary target in air pollution-associated retinal vascular diseases.