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

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 analyzed 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 165 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 (-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 is altered in the iris in PACG.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Iris

SUBMITTER: Pingbo Zhang  

LAB HEAD: Richard D. Semba, M.D.

PROVIDER: PXD022292 | Pride | 2022-03-01

REPOSITORIES: Pride