{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T15:01:20Z","timestamp":1762182080485,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["111-2635-B-418-001"],"award-info":[{"award-number":["111-2635-B-418-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Background: Neuromyelitis optica spectrum disorder (NMOSD) causes severe optic nerve (ON) inflammation and vision loss. Current treatments remain limited, prompting exploration of new therapeutic strategies. This study evaluated the efficacy of ITRI-E-(S)4046 (ITRI-ES), a dual ROCK1\/2 and MYLK4 kinase inhibitor, in a rat model of NMOSD optic neuritis. Methods: NMOSD-like optic neuritis was induced in rats by applying NMOSD patient serum-soaked sponges around the ON. Rats received intravitreal injections of either 0.2% ITRI-ES, phosphate-buffered saline (PBS), or intraperitoneal methylprednisolone (MP). Visual function was assessed using flash visual-evoked potentials (fVEP). Retinal ganglion cell (RGC) survival and apoptosis were quantified using FluoroGold retrograde labeling and TUNEL assay. ON inflammation and demyelination were evaluated via immunohistochemistry and Western blot analysis of aquaporin-4 (AQP4), myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and inflammatory markers. Results: ITRI-ES significantly preserved visual function, restoring fVEP amplitudes (~36 \u03bcV vs. ~21 \u03bcV in PBS-treated, p &lt; 0.05) and RGC density (~85% of normal vs. ~37% PBS). RGC apoptosis was reduced (~2.3-fold lower vs. PBS, p &lt; 0.05). PBS-treated rats showed decreased AQP4 and MBP (2.5\u20132.8-fold vs. sham) and increased GFAP (2.8-fold). ITRI-ES maintained higher AQP4 (~3.5-fold) and MBP (~1.5-fold) levels, suppressed GFAP (~5.5-fold vs. PBS), reduced NF-\u03baB, IL-1\u03b2, TNF-\u03b1, microglia activation, and macrophage infiltration, and increased anti-inflammatory Arg1 and CD206 markers (~3-fold vs. PBS). Conclusions: ITRI-ES alleviates optic nerve inflammation, preserves retinal integrity, and maintains visual function in NMOSD-associated optic neuritis, underscoring kinase inhibition as a promising therapeutic strategy.<\/jats:p>","DOI":"10.3390\/cells14211712","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1712","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual ROCK1\/2\u2013MYLK4 Kinase Inhibition Preserves Visual Function in a Rat Model of Neuromyelitis Optica Spectrum Disorder Optic Neuritis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8494-7335","authenticated-orcid":false,"given":"Chin-Te","family":"Huang","sequence":"first","affiliation":[{"name":"Institute of Eye Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan"},{"name":"Department of Ophthalmology, Chung Shan Medical University Hospital, Taichung 402306, Taiwan"},{"name":"Department of Ophthalmology, School of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402306, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monir","family":"Hossen","sequence":"additional","affiliation":[{"name":"Institute of Eye Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3075-4642","authenticated-orcid":false,"given":"Tu-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Eye Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Wei","family":"Fu","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 310401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2200-6078","authenticated-orcid":false,"given":"Yi-Hsun","family":"Chen","sequence":"additional","affiliation":[{"name":"Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu 310401, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Lun","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Eye Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan"},{"name":"Department of Ophthalmology, Far Eastern Memorial Hospital, Banqiao District, New Taipei City 220216, Taiwan"},{"name":"Department of Electrical Engineering, Yuan Ze University, Chung-Li, Taoyuan 320315, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8760-5739","authenticated-orcid":false,"given":"Rong-Kung","family":"Tsai","sequence":"additional","affiliation":[{"name":"Institute of Eye Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970473, Taiwan"},{"name":"Institute of Medical Sciences, Tzu Chi University, Hualien 970374, Taiwan"},{"name":"Doctoral Degree Program in Translational Medicine, Tzu Chi University and Academia Sinica, Hualien 970374, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1136\/jnnp-2012-302310","article-title":"Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders","volume":"84","author":"Jacob","year":"2013","journal-title":"J. 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