Role of vasorin, an anti‐apoptotic, anti‐TGF‐β and hypoxia‐induced glycoprotein in the trabecular meshwork cells and glaucoma

• Published in: Journal of cellular and molecular medicine Vol. 26; no. 7; pp. 2063 - 2075
• Main Authors: Choi, Jin A., Maddala, Rupalatha, Karnam, Shruthi, Skiba, Nikolai P., Vann, Robin, Challa, Pratap, Rao, Ponugoti Vasantha
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.04.2022; John Wiley and Sons Inc
• Subjects: Actin; Antigens; Apoptosis; aqueous humour; Blindness; Carrier Proteins - metabolism; Cataracts; Cell activation; Cell death; Cell survival; Cells, Cultured; Cobalt; Cobalt chloride; Enzyme-linked immunosorbent assay; Glaucoma; Glaucoma - metabolism; Glaucoma, Open-Angle - metabolism; Glycoproteins; Glycoproteins - metabolism; Growth factors; Humans; Hypertension; Hypoxia; Hypoxia - metabolism; Immunoblotting; Mass spectrometry; Mass spectroscopy; Membrane Proteins - metabolism; ocular hypertension; Original; Patients; Peptides; Proteins; Proteomics; Scientific imaging; Smad2 protein; trabecular meshwork; Trabecular Meshwork - metabolism; Transforming Growth Factor beta2 - metabolism; Transforming growth factor-b; Tumor necrosis factor; vasorin; United States > US; cell survival; ocular hypertension; aqueous humour; glaucoma; vasorin; trabecular meshwork
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.17229

Glaucoma, one of the leading causes of irreversible blindness, is commonly associated with elevated intraocular pressure due to impaired aqueous humour (AH) drainage through the trabecular meshwork. The aetiological mechanisms contributing to impaired AH outflow, however, are poorly understood. Here, we identified the secreted form of vasorin, a transmembrane glycoprotein, as a common constituent of human AH by mass spectrometry and immunoblotting analysis. ELISA assay revealed a significant but marginal decrease in vasorin levels in the AH of primary open‐angle glaucoma patients compared to non‐glaucoma cataract patients. Human trabecular meshwork (HTM) cells were confirmed to express vasorin, which has been shown to possess anti‐apoptotic and anti‐TGF‐β activities. Treatment of HTM cells with vasorin induced actin stress fibres and focal adhesions and suppressed TGF‐β2‐induced SMAD2/3 activation in HTM cells. Additionally, cobalt chloride‐induced hypoxia stimulated a robust elevation in vasorin expression, and vasorin suppressed TNF‐α‐induced cell death in HTM cells. Taken together, these findings reveal the importance of vasorin in maintenance of cell survival, inhibition of TGF‐β induced biological responses in TM cells, and the decreasing trend in vasorin levels in the AH of glaucoma patients suggests a plausible role for vasorin in the pathobiology of ocular hypertension and glaucoma.