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

Int J Mol Sci. 2024 Mar 12;25(6):3229. doi: 10.3390/ijms25063229.

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.

Keywords: HTLV-1 uveitis; Rho-associated coiled coil-forming protein kinase inhibitor; glaucoma; human T-cell leukemia virus type 1; ocular inflammation; ripasudil.

MeSH terms

  • Adult
  • Cytokines / therapeutic use
  • Glaucoma* / drug therapy
  • Glaucoma* / etiology
  • Human T-lymphotropic virus 1*
  • Humans
  • Interleukin-6
  • Isoquinolines*
  • NF-kappa B
  • Sulfonamides*
  • Uveitis*
  • rho-Associated Kinases

Substances

  • K-115
  • NF-kappa B
  • Cytokines
  • Interleukin-6
  • rho-Associated Kinases
  • Isoquinolines
  • Sulfonamides