Bioactive ATX/LPA/LPC concentrations were present in aqueous humor, and higher ATX and LPA concentrations were significantly correlated with IOP in all study subjects. Furthermore, the ATX-LPA pathway was significantly related to glaucoma subtype. These results reveal the potentially important role of the ATX-LPA pathway for IOP regulation in healthy subjects and glaucoma patients.

The results of this study, including the robust induction of ATX by Dex treatment, in association with fibrotic changes and ECM production in HTM cells, collectively suggest a potential role for ATX-LPA pathway in the regulation of aqueous humor outflow and IOP in glaucomatous eyes.

PurposeThe purpose of the current study is to investigate the test-retest reproducibility of visual fields (VFs) measured with the MP-3 microperimeter, in patients with retinitis pigmentosa (RP).MethodVFs were twice measured with the MP-3 and also the Humphrey Field Analyzer, using the 10–2 test grid pattern in both perimeters, in 30 eyes (15 right and 15 left eyes) of 18 RP patients (11 males and 7 females). Test-retest reproducibility was assessed using the mean absolute deviation (MAD) measure at all 68 points in the test grid. Reproducibility was also evaluated using the intraclass correlation coefficient (ICC) of VF sensitivities.ResultThe mean sensitivity measured in the HFA 10–2 was significantly higher than that measured in the MP-3 in both the first and second VF tests (p <0.0001, linear mixed model). The MAD was 2.4±0.6 [1.1 to 3.6] dB for MP-3 and 2.4±0.9 [1.1 to 5.1] dB for HFA 10–2, which was not significantly different (p = 0.76, linear mixed model). The ICC value associated with the MP-3 VFs was 0.81±0.13 [0.49 to 0.98], which was significantly larger than that observed for the HFA 10–2 VFs: 0.77±0.19 [0.20 to 0.94] (p = 0.043, linear mixed model).ConclusionThe MP-3 microperimeter appears to be useful to evaluate central visual function in RP eyes, exhibiting test-retest reproducibility that is equal to, or better than, that observed in HFA 10–2 VFs.

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.

We explored the potential relevance of aqueous lysophosphatidic acid (LPA) and autotaxin (ATX) levels on postoperative outcomes of trabeculectomy, and the effects of ATX on fibrotic response in cultured human conjunctiva fibroblast (HCF) cells. We enrolled 70 glaucomatous eyes which underwent trabeculectomy, and quantified aqueous LPA and ATX. Those eyes were followed up for 12 months, and postoperative filtering blebs were evaluated using anterior segment optical coherence tomography. Also, the ATX-induced fibrotic changes in HCFs and the effects of an ATX inhibitor were assessed. Measured aqueous ATX and LPA levels were significantly different between glaucoma subtypes. In multivariate analyses, aqueous ATX levels were significantly correlated with the presence of needlings at 1, 3, 6 and 12 months after surgery. Exfoliative glaucoma, whose ATX level was significantly high, showed significantly increased numbers of needlings and a lower cumulative success rate without needlings. An in vitro study showed that fibrotic changes were upregulated by ATX treatment in HCFs, which was significantly suppressed by an ATX inhibitor. We presently demonstrate that aqueous ATX may be a prognostic factor affecting the fibrotic response in HCFs and bleb formation, and inhibition of ATX could be a therapeutic target after trabeculectomy.