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 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.

Global and Comparative Proteome Signatures in the Lens Capsule, Trabecular Meshwork, and Iris of Patients With Pseudoexfoliation Glaucoma

“…The use of “omics” for disease pathogenesis or staging is not new and has been studied in several groups ( Wang-Su et al, 2003 ; Bai et al, 2020 ; Rao et al, 2021 ; Semba et al, 2021 ). Multiomics studies will enable significant progress in the understanding of disease at multiple levels in the coming years, which are as follows: i) identification of biomarkers to be used in the diagnosis or prognosis of the disease, ii) advancement in the knowledge of possible physiopathological mechanisms, and iii) development of new and effective therapeutic strategies.…”

“…Wang-Su et al reported an abundance of αA-, αB-, and βB2-crystallins in both freshly isolated and cultured human lens epithelial (HLE) cells ( Wang-Su et al, 2003 ). Semba et al concluded that the ECM composition and homeostasis are altered in the iris in primary closed-angle glaucoma (PACG) through a high-throughput proteomics approach ( Semba et al, 2021 ). The practice of multiomics research in the ocular tissues of neurological disorders and other pathological conditions has gained momentum with advanced technological techniques ( Wang-Su et al, 2003 ; Vogeser and Seger, 2008 ; Sethi and Zaia, 2017 ; Bai et al, 2020 ; Semba et al, 2021 ).…”

“…Semba et al concluded that the ECM composition and homeostasis are altered in the iris in primary closed-angle glaucoma (PACG) through a high-throughput proteomics approach ( Semba et al, 2021 ). The practice of multiomics research in the ocular tissues of neurological disorders and other pathological conditions has gained momentum with advanced technological techniques ( Wang-Su et al, 2003 ; Vogeser and Seger, 2008 ; Sethi and Zaia, 2017 ; Bai et al, 2020 ; Semba et al, 2021 ). Furthermore, a recent study by Alicia De Maria et al found that fibrillin-1, latent transforming growth factor-β-binding protein-2, latent transforming growth factor-β-binding protein-3, and lysyl oxidase-like 1 were abundant in the exfoliative material constituent of the human lens capsule specimen by mass spectrometry (2D-LC/MS) analysis.…”

Creation of a Plant Metabolite Spectral Library for Untargeted and Targeted Metabolomics

“…Based on the high-resolution Orbitrap data, the sequentially stepped targeted MS/MS (sst-MS/MS) method was developed for targeted peptide analysis. After acquiring global comparative proteomics data using Q-Exactive Plus mass spectrometer, 32 changed proteins were validated using the SRM of selected peptides that were unique to those proteins [34]. Similarly, Gu et al used globally optimized targeted MS for metabolomics that combined the advantages of targeted detection and untargeted profiling with an LC−triple quadrupole MS [35].…”

Thrombospondin-1 Signaling Through the Calreticulin/LDL Receptor Related Protein 1 Axis: Functions and Possible Roles in Glaucoma

“…So what role might these functions of the NTD of TSP-1 play in the pathologic changes to ocular tissue structure in glaucoma? Multiple studies suggest that TSP-1 expression is variably increased in the glaucomatous TM and in the (LC of the optic nerve head and sclera at the posterior of the eye (Tripathi et al, 1991;Hiscott et al, 1996;Flugel-Koch et al, 2004;Rhee et al, 2009;Chatterjee et al, 2014;Semba et al, 2021). Furthermore, knockout of the Thbs1 gene in mice reduces intra-ocular pressure (Haddadin et al, 2012).…”