Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris

Richard D. Semba, Pingbo Zhang, Craig Dufresne, Tianshun Gao, Ibrahim Al-Jadaan, Earl R. Craven, Jiang Qian, Deepak P. Edward, Alka Mahale

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: To characterize the proteome of the iris in primary angle closure glaucoma (PACG). Experimental Design: In this cross-sectional study, iris samples were obtained from surgical iridectomy of 48 adults with PACG and five normal controls. Peptides from iris were analysed using liquid chromatography-tandem mass spectrometry on an Orbitrap Q Exactive Plus mass spectrometer. Verification of proteins of interest was conducted using selected reaction monitoring on a triple quadrupole mass spectrometer. The main outcome was proteins with a log2 two-fold difference in expression in iris between PACG and controls. Results: There were 3,446 non-redundant proteins identified in human iris, of which 416 proteins were upregulated and 251 proteins were downregulated in PACG compared with controls. Thirty-two upregulated proteins were either components of the extracellular matrix (ECM) (fibrillar collagens, EMILIN-2, fibrinogen, fibronectin, matrilin-2), matricellular proteins (thrombospondin-1), proteins involved in cell-matrix interactions (integrins, laminin, histidine-rich glycoprotein, paxillin), or protease inhibitors known to modulate ECM turnover (α-2 macroglobulin, tissue factor pathway inhibitor 2, papilin). Two giant proteins, titin and obscurin, were up- and down-regulated, respectively, in the iris in PACG compared with controls. Conclusions and Clinical Relevance: This proteomic study shows that ECM composition and homeostasis are altered in the iris in PACG.

Original languageEnglish (US)
Article number2000094
JournalProteomics - Clinical Applications
Volume15
Issue number6
DOIs
StatePublished - Nov 2021

Keywords

  • extracellular matrix
  • eye
  • iris
  • primary angle closure glaucoma
  • proteomics

ASJC Scopus subject areas

  • Clinical Biochemistry

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