Decrease of Prolylcarboxypeptidase Dose of Aqueous Humor is Involved in the Pathogenesis of Primary Open-Angle Glaucoma via Finetuning of the Local Ocular Renin-Angiotensin System.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS

ACS Applied Bio Materials Pub Date : 2024-10-29 eCollection Date: 2024-10-01 DOI:10.1177/15593258241298062

Jing Ren, Yuanyuan Xiao, Di Wang, Huiling Cui, Rumeng Zhao, Zilu Guo, Yuhao Wang, Shichao Zhu, Bo Tang, Jing Wang, Gang Wang, Huaying Wang, Xinyuan Hu, Rick F Thorne, Shichao Duan, Haijun Li

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Abstract

Objective: In this study, we investigated the cause of the AngII dose elevation in aqueous humor of primary open-angle glaucoma (POAG) patients.

Methods: Enzyme-linked immunosorbent assay (ELISA), western blotting were used to detect concentration of Angiotensin Converting Enzyme 2 (ACE2) and Prolylcarboxypeptidase (PRCP). AngII and AngII + Recombinant PRCP were injected into anterior chamber of mouse eye. Mouse Intraocular pressure (IOP) was measured every week, mouse eye sections were conducted Hematoxylin-and-Eosin (H&E) staining, Masson' staining and Immunofluorescence staining. Western blotting and Immunofluorescence staining assays to detected fibrosis of trabecular meshwork cells. Mass spectrometry was used to identify proteins of aqueous humor.

Results: PRCP dose are decreased in aqueous humor of POAG patients. There is a negative correlation between PRCP and AngII levels in aqueous humor and between PRCP levels and the IOP. PRCP treatment reverses fibrosis of trabecular meshwork (TM) and prevents IOP elevation induced by AngII. Exogenous PRCP rescues fibrosis induced by AngII in HTMCs. Proteome profiling detected 502 differentially expressed proteins.

Conclusion: Our study found PRCP dose was decreased in POAG patients' aqueous humor, and it might cause high level of AngII. Restoration of PRCP rescued fibrosis of TM cells and ameliorated IOP in AngII treatment mouse.

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通过微调局部眼部肾素-血管紧张素系统，降低水液中的前羧肽酶剂量参与原发性开角型青光眼的发病机制

研究目的本研究探讨了原发性开角型青光眼（POAG）患者房水中AngII剂量升高的原因：方法：采用酶联免疫吸附试验（ELISA）和免疫印迹法检测血管紧张素转换酶2（ACE2）和羧酸原肽酶（PRCP）的浓度。将 AngII 和 AngII + 重组 PRCP 注入小鼠眼球前房。每周测量小鼠眼压（IOP），并对小鼠眼球切片进行苏木精-伊红（H&E）染色、Masson'染色和免疫荧光染色。用 Western 印迹和免疫荧光染色检测小梁网细胞的纤维化。质谱法用于鉴定房水中的蛋白质：结果：POAG 患者的眼房水中 PRCP 剂量降低。结果：PRCP剂量在POAG患者的眼房水中降低，PRCP与眼房水中AngII的水平呈负相关，PRCP水平与眼压呈负相关。PRCP治疗可逆转小梁网（TM）的纤维化，并防止AngII诱导的眼压升高。外源性PRCP可挽救血管紧张素II诱导的高密度脂蛋白胆固醇细胞纤维化。蛋白质组分析检测到了502种不同表达的蛋白质：我们的研究发现，POAG 患者眼房水中 PRCP 的剂量降低，可能导致 AngII 水平升高。恢复 PRCP 可挽救 TM 细胞的纤维化，并改善 AngII 治疗小鼠的眼压。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

ACS Applied Bio Materials Chemistry-Chemistry (all)

CiteScore

9.40

自引率

2.10%

发文量

464