Involvement of autotaxin in the pathophysiology of elevated intraocular pressure in Posner-Schlossman syndrome
Involvement of autotaxin in the pathophysiology of elevated intraocular pressure in Posner-Schlossman syndrome
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DOI：
10.1038/s41598-020-63284-1
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发表时间：
2020-04-14
影响因子：
4.6
通讯作者：
Aihara, Makoto
中科院分区：
文献类型：
--
作者：
Igarashi, Nozomi;Honjo, Megumi;Aihara, Makoto
目的：研究房水中的自体趋化因子(ATX)是否会导致Posner-Schlossman综合征(PSS)患者的眼压升高。对PSS患者房水中ATX和转化生长因子-β(TGF-β)进行定量检测。检测巨细胞病毒(CMV)感染的人小梁细胞(HTM)中ATX和转化生长因子-β(TGF-β)的表达。用巨细胞病毒感染的HTM细胞的条件培养液培养HTM细胞和猴Schlemm氏管内皮细胞，观察其生物学变化。CMV阳性PSS患者房水中ATX和转化生长因子-β1表达上调，且房水中ATX水平与眼压呈正相关。CMV感染可上调HTM细胞ATX和转化生长因子-β1的表达。条件培养液诱导HTM细胞发生纤维化改变，并降低姐妹染色单体互换的通透性，这一作用可被ATX抑制剂、溶血磷脂酸受体拮抗剂和Rho激酶抑制剂所减弱。CMV感染所致房水中的ATX可引起高眼压。调节ATX活性可能是治疗PSS的一种新方法。
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-beta) in the aqueous humor were quantified in PSS patients. The expression of ATX and TGF-beta 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-beta 1 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-beta 1 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.