Ripasudil as a Potential Therapeutic Agent in Treating Secondary Glaucoma in HTLV-1-Uveitis: An In Vitro Analysis

Author:

Yang Mingming1,Kamoi Koju1,Zong Yuan1,Zhang Jing1,Zou Yaru1ORCID,Ohno-Matsui Kyoko1

Affiliation:

1. Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan

Abstract

Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5–10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.

Funder

JSPS KAKENHI

Ministry of Health, Labor, and Welfare of Japan

Japan Agency for Medical Research and Development, AMED

Takeda Science Foundation

Publisher

MDPI AG

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