Tauroursodeoxycholic Acid Mitigates Inflammation, ER Stress, and Apoptosis in Experimental Endotoxin-Induced Uveitis: In Vivo and In Vitro Evidence.

Endotoxin-induced uveitis (EIU) is a well-established model for acute ocular inflammation and mimics aspects of human uveitis. Tauroursodeoxycholic acid (TUDCA), a bile acid with known anti-inflammatory and cytoprotective properties, may attenuate retinal injury by targeting endoplasmic reticulum (ER) stress and apoptosis. This study investigates the protective effects of TUDCA in both in vivo and in vitro EIU models. EIU was induced in male Wistar rats by intravitreal injection of lipopolysaccharide (LPS), with or without prior intraperitoneal TUDCA administration. ARPE-19 cells were used to model retinal pigment epithelial stress in vitro. Ocular inflammation was assessed clinically and histologically. Immunostaining and immunofluorescence quantified ER stress marker Glucose-Regulated Protein 78 (GRP78), caspase-3, caspase-12, and apoptosis. Caspase-3 activity and TUNEL assays evaluated apoptotic response. TUDCA pretreatment significantly reduced LPS-induced ocular inflammation and retinal thickening in rats. In ARPE-19 cells, TUDCA restored LPS-compromised viability and mitigated morphological damage. Both models showed reduced expression of GRP78, caspase-3, and caspase-12 following TUDCA administration. TUNEL and caspase-3 activity assays confirmed that TUDCA decreased apoptosis in retinal tissues and cultured cells. The findings demonstrate that TUDCA effectively suppresses ER stress and apoptosis pathways activated during endotoxin-induced retinal inflammation. Its dual anti-inflammatory and cytoprotective actions support its therapeutic potential in acute ocular inflammatory conditions. TUDCA attenuates clinical, histological, and molecular manifestations of LPS-induced uveitis, highlighting its promise as a candidate for adjunctive therapy in inflammatory retinal diseases.