Role of the autotaxin-lysophosphatidic acid axis in glaucoma, aqueous humor drainage and fibrogenic activity

This study reports a significant increase in the levels of autotaxin, lysophosphatidylcholine (LPC), LPA and connective tissue growth factor (CTGF) in the AH of Caucasian and African American open angle glaucoma patients relative to age-matched non-glaucoma patients. Treatment of human TM cells with dexamethasone, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) increased the levels of autotaxin protein, a response that was mitigated by inhibitors of glucocorticoid receptor, NF-kB and SMAD3. Dexamethasone, TNF-α, IL-1β and LPC treatment of TM cells also led to an increase in the levels of CTGF, fibronectin and collagen type 1 in an autotaxin dependent manner. Additionally, in perfused enucleated mouse eyes, autotaxin and LPC were noted to decrease, while inhibition of autotaxin was increased aqueous outflow through the TM. Taken together, these results provide additional evidence for dysregulation of the autotaxin-LPA axis in the AH of glaucoma patients, reveal molecular insights into the regulation of autotaxin expression in TM cells and the consequences of autotaxin inhibitors in suppressing the fibrogenic response and resistance to AH outflow through the TM.
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research

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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: eLife - Category: Biomedical Science Tags: Developmental Biology Human Biology and Medicine Source Type: research
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Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
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Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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Source: The British Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Br J Ophthalmol Source Type: research
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Source: Experimental Eye Research - Category: Opthalmology Authors: Tags: Exp Eye Res Source Type: research
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Source: The British Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Br J Ophthalmol Source Type: research
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Source: The British Journal of Ophthalmology - Category: Opthalmology Authors: Tags: Br J Ophthalmol Source Type: research
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