We previously reported that autotaxin (ATX), a lysophosphatidic acid (LPA) -producing enzyme, is present in high levels in anterior chamber aqueous humor in all glaucoma types, influences the fibrosis of trabecular meshwork (TM), and is involved in elevated intraocular pressure. This study focused on patients with Posner-Schlossman syndrome (PSS) with cytomegalovirus (CMV) -positivity in anterior chamber aqueous humor and examined the involvement of the concentrations of ATX in anterior chamber aqueous humor and transforming growth factor (TGF)-β, which has previously been suggested to be involved in the pathology of open angle glaucoma, in elevated intraocular pressure. The expression of both ATX and TGF-β1 increased in the anterior chamber aqueous humor of patients with CMV-positive PSS; ATX concentration levels positively correlated with intraocular pressure. In addition, when human TM cells (hTMs) were infected with CMV, the expression of both ATX and TGF-β1 increased. When the culture supernatant of hTMs infected with CMV was produced as a conditioned medium and added to hTMs and monkey Schlemm canal endothelial cells (SCEs), the fibrosis of hTMs was promoted and the outflow resistance of SCEs was increased. These changes were suppressed by the addition of ATX inhibitors, LPA receptor antagonists, and Rho-associated protein kinase (ROCK) inhibitors. The results suggest that CMV infection increases ATX concentration in the anterior chamber aqueous humor, causing elevated intraocular pressure via TM fibrosis and increased outflow resistance. Furthermore, suppression of the ATX-LPA pathway and downstream signaling may represent a new therapeutic target for PSS.
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 126: 933-940,2022.