{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T15:52:11Z","timestamp":1777737131048,"version":"3.51.4"},"reference-count":34,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T00:00:00Z","timestamp":1776816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Mechanical stress has been implicated in retinal pigment epithelium (RPE) dysfunction and angiogenic signaling in retinal disorders; however, its direct in vivo effects on the RPE\u2013choroid complex remain incompletely understood. Here, we established a mouse model of localized mechanical stress by subconjunctival implantation of glass beads (0.8\u20131.2 mm in diameter) in eight-week-old C57BL\/6J mice to induce transscleral stretching of the RPE. Ocular tissues were analyzed two days after implantation using histological, immunohistochemical, and molecular approaches, and inflammatory mediators were quantified by multiplex cytokine assays. Mechanical stress induced focal serous retinal detachment, elongation of photoreceptor outer segments, and disruption of the RPE tight junction protein ZO-1. VEGF expression in the RPE\u2013choroid complex was significantly upregulated and accompanied by increased levels of inflammatory mediators, including MCP-1. Intravitreal administration of anti-VEGF agents effectively suppressed stress-induced VEGF expression. These findings indicate that mechanical stress is sufficient to induce structural disruption and angiogenic signaling in the RPE in vivo, providing a useful experimental platform for investigating stress-related retinal responses and therapeutic modulation of VEGF signaling.<\/jats:p>","DOI":"10.3390\/biology15090664","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:38:14Z","timestamp":1776854294000},"page":"664","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanical Stress Induces VEGF Expression and RPE Disruption in Mouse Eyes"],"prefix":"10.3390","volume":"15","author":[{"given":"Akira","family":"Minamoto","sequence":"first","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Ae","family":"Ko","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kota","family":"Haruyama","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushige","family":"Ashimori","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Yamaguchi University, Yamaguchi 755-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuhiro","family":"Kimura","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Yamaguchi University, Yamaguchi 755-8505, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1915-1864","authenticated-orcid":false,"given":"Yoshiaki","family":"Kiuchi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hirokazu","family":"Sakaguchi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Science, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Finocchio, L., Zeppieri, M., Gabai, A., Toneatto, G., Spadea, L., and Salati, C. 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