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

• Published in: Proteomics. Clinical applications 2021-11, Vol.15 (6), p.e2000094-n/a
• Main Authors: Semba, Richard D., Zhang, Pingbo, Dufresne, Craig, Gao, Tianshun, Al‐Jadaan, Ibrahim, Craven, Earl R., Qian, Jiang, Edward, Deepak P., Mahale, Alka
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Chromatography, High Pressure Liquid; Collagen; Collagen Type II - metabolism; Connectin; Cross-Sectional Studies; Design of experiments; Down-Regulation; Extracellular matrix; Extracellular Matrix - metabolism; eye; Female; Fibrinogen; Fibronectin; Galactokinase - metabolism; Glaucoma; Glaucoma, Angle-Closure - metabolism; Glaucoma, Angle-Closure - pathology; Glycoproteins; Histidine; Homeostasis; Humans; Integrins; Iris; Iris - metabolism; Iris - surgery; Laminin; Liquid chromatography; Male; Mass spectrometry; Mass spectroscopy; Middle Aged; Paxillin; Peptides; Peptides - analysis; primary angle closure glaucoma; Protease inhibitors; Proteinase inhibitors; Proteins; Proteomes; Proteomics; Quadrupoles; Tandem Mass Spectrometry; Thrombospondin; Tissue factor; Up-Regulation
• ISSN: 1862-8346; 1862-8354
• DOI: 10.1002/prca.202000094

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.