Involvement of autotaxin in the pathophysiology of elevated intraocular pressure in Posner-Schlossman syndrome

Abstract

to examine whether autotaxin (AtX) in the aqueous humor causes elevated intraocular pressure (iop) in patients with posner-Schlossman syndrome (pSS). AtX and transforming growth factor beta (tGf-β) in the aqueous humor were quantified in PSS patients. The expression of ATX and TGF-β in cytomegalovirus (cMV)-infected-human trabecular meshwork (htM) cells was examined. Biological changes in htM cells and monkey Schlemm's canal endothelial (Sce) cells cultured in the conditioned medium of cMV-infected htM cells were analyzed. the expression of AtX and tGf-β1 was upregulated in the aqueous humor of cMV-positive pSS patients, and the level of AtX in the aqueous humor was positively correlated with iop. cMV infection upregulated AtX and tGf-β1 in hTM cells. The conditioned medium induced fibrotic changes in hTM cells and reduced SCE permeability, which was attenuated by an AtX inhibitor, a lysophosphatidic acid receptor antagonist, and a Rho kinase inhibitor. AtX in the aqueous humor induced by cMV infection may trigger elevated iop. Modulating AtX activity may be a novel treatment modality for pSS.

Aqueous autotaxin and TGF-βs are promising diagnostic biomarkers for distinguishing open-angle glaucoma subtypes

“…Higher levels of TGF-β1 and -β3 isoforms are most commonly observed in XFG 28,31 , and it has been speculated that high IOP itself may induce the expression of activated TGF-β1 35 . Taken together with the results of our previous study on PSS 10 , TGF-β1 upregulation may reflect IOP elevation, not as the cause but the result of IOP elevation. As for TGF-β3, Vijay et al 36 reported that TGF-β3 is involved in ECM deposition by applying 1 ng/mL TGF-β3 to hTM cells for 4 weeks.…”

“…In that study, we also found that ATX and TGF-β1 in the AH of PSS patients are significantly correlated. Additionally, our results showed that ATX is significantly related to IOP; however, TGF-β1 is not 10 . In an in vitro study using hTM cells, both ATX and TGF-β1 were significantly upregulated during CMV infection, which mimics SOAG in vitro, whereas TGF-β1 was upregulated following ATX upregulation.…”

“…This suggests the involvement of TGF-β1 in the pathogenesis of increased outflow resistance in XFG, in concordance with the known role of TGF-β1 in stimulating ECM deposition in many fibrotic disorders. However, as for the high levels of TGF-β1 in SOAG, we recently reported that ATX and TGF-β1 were upregulated in the AH in CMV-positive PSS (glaucoma-positive) 10 . In that study, we also found that ATX and TGF-β1 in the AH of PSS patients are significantly correlated.…”

“…in AH were correlated significantly with each other 10 . Therefore, we speculate that crosstalk may exist between ATX and TGF-βs, suggesting that concurrent levels of these mediators may be promising diagnostic biomarkers.…”

Lysophosphatidic Acid and IL-6 Trans-signaling Interact via YAP/TAZ and STAT3 Signaling Pathways in Human Trabecular Meshwork Cells

“…17,[22][23][24][25][26][27][28][29][30][31][32][33][34] For instance, the bioactive lipid, lysophosphatidic acid (LPA), is elevated in the aqueous humor of patients with POAG and other forms of glaucoma. 30,31,35,36 Apart from glaucoma, LPA has been implicated in cancer, fibrosis, and chronic inflammation [37][38][39] ; and typically evokes its biological functions by binding to its G-protein-coupled receptors (i.e., LPAR1 to LPAR6). 33,38 LPA is a catalytic product of autotaxin (ATX), whose enzymatic activity and/or expression levels are also increased in POAG and mechanically stretched human TM (hTM) cells.…”