Taurine mechanism in preventing retinal cell damage from acute ocular hypertension through GTPBP3 regulation

Wei Lu; Yuting Yang; Shunxiang Gao; Jihong Wu; Xinghuai Sun

doi:10.1016/j.exer.2024.110222

Taurine mechanism in preventing retinal cell damage from acute ocular hypertension through GTPBP3 regulation

Exp Eye Res. 2024 Dec 20:110222. doi: 10.1016/j.exer.2024.110222. Online ahead of print.

Authors

Wei Lu¹, Yuting Yang¹, Shunxiang Gao¹, Jihong Wu¹, Xinghuai Sun²

Affiliations

¹ Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
² Department of Ophthalmology & Visual Science, Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institutes of Brain Science, Fudan University, Shanghai 200032, China; NHC Key Laboratory of Myopia, Chinese Academy of Medical Sciences, and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai 200031. Electronic address: xhsun@shmu.edu.cn.

PMID: 39710098
DOI: 10.1016/j.exer.2024.110222

Abstract

We aimed to explore the protective effects and underlying mechanisms of taurine on retinal cells during acute ocular hypertension (AOH)-induced damage. Retinal morphology, apoptosis, mitochondrial structure, electroretinography, expression of GTP binding protein 3 (GTPBP3), and molecules in the unfolded protein response (UPR) were examined in an AOH mouse model and wild-type (WT) mice with or without intravitreal injection of taurine. For in vitro experiments, the GTPBP3 expression and endoplasmic reticulum (ER) stress were examined in R28 cell line under hydrogen peroxide (H₂O₂)-induced damage or hypoxia/reoxygenation (H/R)-induced damage, with or without taurine pretreatment. Taurine pretreatment alleviated retinal damage caused by AOH modeling. The GTPBP3 expression level decreased after AOH injury, and taurine pretreatment reversed this reduction. Retinas with decreased GTPBP3 expression showed reduced retinal ganglion cell (RGC) function, which could be reversed by intravitreal taurine injection. In H₂O_2-, H/R-, and AOH-induced damage, UPR were activated and alleviated by taurine pretreatment. GTPBP3 knockdown in R28 cells also activated the UPR, which was alleviated by taurine. A UPR activator downregulated GTPBP3 levels in normal R28 cells, whereas a UPR inhibitor upregulated GTPBP3 levels in GTPBP3 knockdown R28 cells. In conclusion, this study provides important evidence that taurine prevents retinal cell damage in mice exposed to AOH and modulates GTPBP3 expression via the UPR pathway. Interventions targeting this mechanism can be used as potential therapeutic targets for AOH damage.

Keywords: Acute ocular hypertension; GTPBP3; Mitochondria; Taurine; Unfolded protein response.