Airborne fine particulate matter (PM_2.5) 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 (PM_2.5) exposure on the inner blood-retinal barrier (iBRB). In this study, retinal vascular permeability and diameter were enhanced in the PM_2.5-exposed animal model (1 mg/mL PM_2.5, 10 μL per eye, 4 times per day, 3 days), together with observable retinal edema and increased inflammation level in retina. PM_2.5-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 PM_2.5 exposure (25, 50, and 100 μg/mL PM_2.5 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 PM_2.5-induced cytotoxicity of HRMECs. The present study investigated the in vivo effects of PM_2.5 on retinas, revealing that PM_2.5 exposure induced retinal inflammation, vascular dilatation, and caused damage to the iBRB. The crucial role of ferroptosis was discovered during PM_2.5-induced HRMEC cytotoxicity and dysfunction, indicating a potential precautionary target in air pollution-associated retinal vascular diseases.