Role of vasorin,an anti‐apoptotic,anti‐TGF‐β and hypoxia‐induced glycoprotein in the trabecular meshwork cells and glaucoma |
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Authors: | Jin A Choi Rupalatha Maddala Shruthi Karnam Nikolai P Skiba Robin Vann Pratap Challa Ponugoti Vasantha Rao |
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Institution: | 1. Department of Ophthalmology, Duke University School of Medicine, Durham North Carolina, USA ; 2. Department of Ophthalmology, College of Medicine, St. Vincent’s Hospital, The Catholic University of Korea, Seoul Korea ; 3. Department of Pharmacology and Cancer Biology, Duke University School of Medicine, Durham North Carolina, USA ;4.Present address: University of California, Berkley California, USA |
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Abstract: | 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. |
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Keywords: | aqueous humour cell survival glaucoma ocular hypertension trabecular meshwork vasorin |
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