TYRP1 通过与 PMEL 结合保护视网膜神经节细胞免于凋亡和氧化应激。

TYRP1 Protects Against the Apoptosis and Oxidative Stress of Retinal Ganglion Cells by Binding to PMEL.

机构信息

Tianjin Eye Hospital, Tianjin Key Laboratory of Ophthalmology and Vision Science, Nankai University Eye Hospital, Clinical College of Ophthalmology, Tianjin Medical University, Tianjin, P.R. China.

Tianjin Key Laboratory of Retinal Functions and Diseases, Tianjin Branch of National Clinical Research Center for Ocular Disease, Eye Institute and School of Optometry, Tianjin Medical University Eye Hospital, Tianjin, P.R. China.

出版信息

Ocul Immunol Inflamm. 2023 Jul;31(5):1024-1034. doi: 10.1080/09273948.2022.2081862. Epub 2022 Jun 16.

DOI:10.1080/09273948.2022.2081862

PMID:35708352

Abstract

OBJECTIVES

This research aimed to dissect the function of TYRP1 and PMEL in glaucomatous animal and cell models.

METHODS

A chronic ocular hypertension (COH) rat model was induced in the right eyes of rats through the electrocoagulation of superficial iris veins. In addition, an oxygen-glucose deprivation (OGD)-retinal ganglion cell (RGC) model was constructed through OGD. TYRP1 and PMEL expression was altered in the animal and cell models to explore their effects.

RESULTS

TYRP1 and PMEL expression was poor in glaucoma patients, COH rats, and OGD-RGCs. Mechanistically, TYRP1 interacted with PMEL to upregulate PMEL in OGD-RGCs. TYRP1 overexpression enhanced viability and diminished apoptosis and oxidative stress of OGD-RGCs, which was abolished by PMEL knockdown. TYRP1 upregulation reduced intraocular pressure, RGC apoptosis, and oxidative stress in COH rats, which was reversed by PMEL knockdown.

CONCLUSIONS

TYRP1 elevates PMEL expression to reduce RGC apoptosis and oxidative stress in vivo and in vitro.

摘要

目的

本研究旨在剖析 TYRP1 和 PMEL 在青光眼动物和细胞模型中的作用。

方法

通过对浅层虹膜静脉进行电凝，在大鼠右眼诱导慢性眼压升高（COH）模型。此外，通过氧葡萄糖剥夺（OGD）构建视网膜神经节细胞（RGC）模型。改变动物和细胞模型中的 TYRP1 和 PMEL 表达，以探讨其作用。

结果

青光眼患者、COH 大鼠和 OGD-RGCs 中 TYRP1 和 PMEL 的表达较差。在机制上，TYRP1 与 PMEL 相互作用，上调 OGD-RGCs 中的 PMEL。TYRP1 过表达增强了 OGD-RGCs 的活力，减少了细胞凋亡和氧化应激，而 PMEL 敲低则消除了这种作用。TYRP1 的上调降低了 COH 大鼠的眼内压、RGC 凋亡和氧化应激，而 PMEL 敲低则逆转了这种作用。