Evaluation of the effects of tauroursodeoxycholic acid on ocular inflammation in an experimental rat uveitis model and ARPE-19 cell culture

Purpose: Endotoxin-induced uveitis (EIU) is a widely recognised experimental model of acute ocular inflammation, that mimics certain features of human uveitis. Tauroursodeoxycholic acid (TUDCA), a bile acid known for its anti-inflammatory and cytoprotective properties, may alleviate retinal damage by modulating endoplasmic reticulum (ER) stress and apoptosis pathways. This study aims to investigate the protective effect of TUDCA both in vivo and in vitro in EIU models. Materials and Methods: EIU was induced in male Wistar rats by intravitreal injection of lipopolysaccharide (LPS), with a subset of animals previously treated intraperitoneally with TUDCA. ARPE-19 cells were used to model the stress of the retinal pigment epithelium in vitro. Clinical and histopathological examinations evaluated the ocular inflammation. Immunohistochemistry and immunofluorescence staining were used to detect the ER stress marker glucose-regulated protein 78 (GRP78), caspase-3, caspase-12, and apoptosis. Caspase-3 activity assays and TUNEL staining were used to further quantify the apoptotic response. Results: Pretreatment with TUDCA significantly reduced LPS-induced ocular inflammation and retinal thickening in rats. In ARPE-19 cells, TUDCA restored the viability of cells impaired by LPS exposure and ameliorated morphological damage. Both in vivo and in vitro models showed decreased expression of GRP78, caspase-3, and caspase-12 after TUDCA administration. TUNEL and caspase-3 assays confirmed the reduced apoptosis after treatment. Discussion: These results show that TUDCA effectively suppresses ER stress and apoptotic signalling pathways activated during inflammation. Its combined anti-inflammatory and cytoprotective effects argue in favour of considering TUDCA as a potential therapeutic candidate in ocular inflammatory diseases. Conclusions: In the EIU model, TUDCA significantly suppresses the inflammatory response at clinical, histopathological, and molecular levels. Keywords: Apoptosis, Endoplasmic Reticulum (ER) Stress, Endotoxin-Induced Uveitis (EIU), Inflammation, Tauroursodeoxycholic Acid (TUDCA)