TY - JOUR
T1 - Primary angle closure glaucoma is characterized by altered extracellular matrix homeostasis in the iris
AU - Semba, Richard D.
AU - Zhang, Pingbo
AU - Dufresne, Craig
AU - Gao, Tianshun
AU - Al-Jadaan, Ibrahim
AU - Craven, Earl R.
AU - Qian, Jiang
AU - Edward, Deepak P.
AU - Mahale, Alka
N1 - Funding Information:
This study was supported the Joint King Khaled Eye Specialist Hospital and Wilmer Eye Institute Research Grant Program, NIH grants R01 EY024596 and R01 AG027012, and Research to Prevent Blindness.
Publisher Copyright:
© 2021 Wiley-VCH GmbH
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - extracellular matrix
KW - eye
KW - iris
KW - primary angle closure glaucoma
KW - proteomics
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U2 - 10.1002/prca.202000094
DO - 10.1002/prca.202000094
M3 - Article
C2 - 34240827
AN - SCOPUS:85111009915
SN - 1862-8346
VL - 15
JO - Proteomics - Clinical Applications
JF - Proteomics - Clinical Applications
IS - 6
M1 - 2000094
ER -