Dose-Response (Oct 2024)

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

  • 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

DOI
https://doi.org/10.1177/15593258241298062
Journal volume & issue
Vol. 22

Abstract

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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.