{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T23:14:39Z","timestamp":1790637279013,"version":"4.1.0"},"reference-count":28,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"unspecified","delay-in-days":26,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Grant-in-Aid for Scientific Research","award":["23K09036"],"award-info":[{"award-number":["23K09036"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open Ophth"],"accepted":{"date-parts":[[2025,2,8]]},"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Rho-associated protein kinases (ROCKs) are a key regulator of T cell function, influencing a wide range of processes from activation to differentiation. Experimental autoimmune uveoretinitis (EAU) is an animal model of human non-infectious uveitis. This study aimed to evaluate the suppressive effects of ripasudil, a ROCK inhibitor, on ocular inflammation when administered from the onset of EAU and to elucidate the underlying mechanisms of its inhibitory effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>EAU was induced in wild-type C57BL\/6 mice by immunisation with IRBP peptide. Ripasudil or its vehicle, PBS, was intraperitoneally administered daily starting from 8\u2009days post-immunisation. Clinical and histopathological examinations and analysis of T cell activation state were conducted. In addition, T cell gene expression profiles in the relevant immune functions were identified using single-cell RNA sequencing (scRNA-seq).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The development of EAU was significantly attenuated and T cell activation and Th1 cell differentiation were significantly inhibited in mice with ripasudil (RIP-EAU) compared with mice with PBS (PBS-EAU), scRNA-seq using splenic T cells indicated that genes involved in the ROCK signalling pathway were highly expressed in low-differentiated Th1\/Th17 cells, intermediate Th1 cells and differentiated Th1 cells. In addition, although differentiated Th1 and Th17 cells constituted similar proportions between PBS-EAU and RIP-EAU mice, RIP-EAU mice exhibited fewer low-differentiated Th1\/Th17 cells and intermediate Th1 cells compared with PBS-EAU mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ripasudil suppressed EAU when administered from the onset of the disease by inhibiting cells that strongly express genes involved in the ROCK signalling pathway and differentiate into Th1 cells.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjophth-2024-001981","type":"journal-article","created":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T23:15:20Z","timestamp":1740698120000},"page":"e001981","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":6,"title":["Anti-inflammatory actions of ripasudil ameliorate experimental autoimmune uveoretinitis in the acute phase"],"prefix":"10.1136","volume":"10","author":[{"given":"Kozo","family":"Harimoto","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, National Defense Medical College, Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Nishio","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Defense Medical College, Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Someya","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Defense Medical College, Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohito","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Defense Medical College, Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masataka","family":"Ito","sequence":"additional","affiliation":[{"name":"Developmental Anatomy and Regenerative Biology, National Defense Medical College, Tokorozawa, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4913-7089","authenticated-orcid":false,"given":"Masaru","family":"Takeuchi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, National Defense Medical College, Tokorozawa, Saitama, 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