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

Nozomi Igarashi,Yutaka Yatomi,Reiko Yamagishi,Megumi Honjo,Toshikatsu Kaburaki,Makoto Aihara,Makoto Kurano,Koji Igarashi

doi:10.1038/s41598-020-63284-1

Nozomi Igarashi, Yutaka Yatomi + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-63284-1

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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.

Highlights

Glaucoma is the second leading cause of blindness globally
Of the 19 eyes from 19 CMV-positive Posner-Schlossman syndrome (PSS) patients in this study, 9 eyes were diagnosed as having SOAG, i.e., PSS (CMV+/SOAG+); and 10 eyes were CMV-positive without SOAG, PSS (CMV+/SOAG−)
There was no significant difference in intraocular pressure (IOP) among the three groups, the number of glaucoma eye drops used was significantly different: 0.3 ± 0.5 for PSS (CMV-/ SOAG−), 0.7 ± 0.7 for PSS (CMV+/SOAG−), and 2.3 ± 1.0 for PSS (CMV+/SOAG+) (Table 1)

Summary

Introduction

Glaucoma is the second leading cause of blindness globally It is characterized by a marked increase in intraocular pressure (IOP) that causes damage to the optic nerve[1,2,3]. PSS causes a higher rate of elevated IOP compared to other types of uveitis, and the rate of glaucomatous optic neuropathy is reported to be as high as 45%12,13. PSS is characterized by unilateral anterior uveitis (AU), causing recurrent attacks of marked IOP elevation[13]. It has been reported that cytomegalovirus (CMV) has a strong association with PSS, with up to 52.2% of PSS patients testing positive for CMV18,20. Anti-glaucoma agents, and ganciclovir can control inflammation and the elevation of IOP in most PSS cases; some patients are resistant to treatment and must undergo. CMV-positive PSS patients are more likely to have refractive symptoms and undergo operations including filtration surgery compared to CMV-negative PSS patients[19]

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