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The change of scleral morphology in experimental myopic guinea pigs was observed by transmission electron microscopy, Masson staining, and TUNEL assay, respectively. Meanwhile, the levels of the PI3K\/AKT signaling pathway- and scleral remodeling-related molecules in scleral tissues were determined by real-time quantitative PCR (qPCR), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, immunohistochemical staining, and western blot, respectively. We found that 2-week myopic induction can elevate PIK3R3 and AKT2 levels and activate the PI3K\/Akt signaling pathway, enhance the expression of E-cadherin and matrix metallopeptidase 2 (MMP2), and decrease the level of transforming growth factor-beta 1 (TGF-\u03b21), tissue inhibitor of matrix metalloproteinase-2 (TIMP2), and collagen (COLI) in the scleral tissue of myopic guinea pigs, thereby leading to scleral remolding. However, 4-week myopic induction could inhibit the PI3K\/AKT signaling pathway and induce apoptosis, accompanied by increased MMP2, E-cadherin, and decreased TGF-\u03b21, TIMP2, and COLI. Results reveal that the disturbed PI3K\/AKT signaling plays a role in scleral remodeling in the experimental myopia through orchestrating apoptosis.<\/jats:p>","DOI":"10.1038\/s41598-025-97643-7","type":"journal-article","created":{"date-parts":[[2025,4,11]],"date-time":"2025-04-11T10:37:42Z","timestamp":1744367862000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Covariation of scleral remodeling and PI3K\/Akt signaling pathway in experimental myopia"],"prefix":"10.1038","volume":"15","author":[{"given":"Xiaomeng","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1712-0055","authenticated-orcid":false,"given":"Lijie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guili","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huixia","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinpeng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yixian","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixue","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuxin","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Liao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6965-9626","authenticated-orcid":false,"given":"Dadong","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongsheng","family":"Bi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,11]]},"reference":[{"key":"97643_CR1","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.preteyeres.2017.09.004","volume":"62","author":"IG Morgan","year":"2018","unstructured":"Morgan, I. 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