Autotaxin induces fibrosis in lamina cribrosa cells in glaucoma
Abstract
Lysophosphatidic acid (LPA) and the enzyme that generates it, autotaxin, have been shown to play a role in fibrosis in the trabecular meshwork in glaucoma, contributing to increased intraocular pressure. We wished to investigate the role of LPA and autotaxin in fibrosis of the lamina cribrosa (LC) of the optic nerve head in glaucoma. LC cells from glaucoma patient donors (GLC) and normal controls (NLC) were cultured, and expression of autotaxin and LPA receptors were determined through real-time quantitative PCR (RT-qPCR), western blotting and immunofluorescence. Autotaxin activity in cell media was measured via a phospholipase assay. GLC cells were treated with an autotaxin inhibitor S32826, and the rate of cell proliferation and ECM gene expression were assessed. GLC cells showed significantly increased autotaxin mRNA (3.84 ± 1.71 fold p < 0.05) and protein expression (1.54 ± 0.41 fold p < 0.05) compared to NLC. The LPA receptor LPA 3 was also significantly overexpressed (2.73 ± 0.23 fold p < 0.001). Treatment of GLC cells with S32826 significantly reduced autotaxin activity, cell proliferation and expression of ECM genes COL1A (0.51±0.06, p < 0.05) and FN1 (0.64±0.12, p < 0.05). Inhibition of autotaxin decreased cell proliferation and ECM production in LC cells, and therefore could be a potential target for fibrosis in the LC in glaucoma.
