Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia

Abstract The present study aimed to investigate the role of the PI3K/Akt signaling pathway in scleral remodeling in the development of negative lens-induced myopia (LIM). The change of scleral morphology in experimental myopic guinea pigs was observed by transmission electron microscopy, Masson stai...

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Main Authors: Xiaomeng Li, Xiaojing Liu, Yingxin Yu, Tuling Li, Lijie Guo, Guili Hu, Huixia Wei, Zhaohui Yang, Jinpeng Liu, Yixian Hao, Ruixue Zhang, Qiuxin Wu, Xuan Liao, Dadong Guo, Hongsheng Bi
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Language:English
Published: Nature Portfolio 2025-04-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-97643-7
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author Xiaomeng Li
Xiaojing Liu
Yingxin Yu
Tuling Li
Lijie Guo
Guili Hu
Huixia Wei
Zhaohui Yang
Jinpeng Liu
Yixian Hao
Ruixue Zhang
Qiuxin Wu
Xuan Liao
Dadong Guo
Hongsheng Bi
author_facet Xiaomeng Li
Xiaojing Liu
Yingxin Yu
Tuling Li
Lijie Guo
Guili Hu
Huixia Wei
Zhaohui Yang
Jinpeng Liu
Yixian Hao
Ruixue Zhang
Qiuxin Wu
Xuan Liao
Dadong Guo
Hongsheng Bi
author_sort Xiaomeng Li
collection DOAJ
description Abstract The present study aimed to investigate the role of the PI3K/Akt signaling pathway in scleral remodeling in the development of negative lens-induced myopia (LIM). 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-β1), 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-β1, TIMP2, and COLI. Results reveal that the disturbed PI3K/AKT signaling plays a role in scleral remodeling in the experimental myopia through orchestrating apoptosis.
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spelling doaj-art-35a3b7e4b9624d29890e8000dfbbc0842025-08-20T02:17:09ZengNature PortfolioScientific Reports2045-23222025-04-0115111510.1038/s41598-025-97643-7Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopiaXiaomeng Li0Xiaojing Liu1Yingxin Yu2Tuling Li3Lijie Guo4Guili Hu5Huixia Wei6Zhaohui Yang7Jinpeng Liu8Yixian Hao9Ruixue Zhang10Qiuxin Wu11Xuan Liao12Dadong Guo13Hongsheng Bi14Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineGuangzhou laboratory, Guangzhou Medical UniversityShandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineShandong University of Traditional Chinese MedicineAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineDepartment of Ophthalmology of Affiliated Hospital and Medical School of Ophthalmology and Optometry, North Sichuan Medical CollegeShandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular DiseasesAffiliated Eye Hospital of Shandong University of Traditional Chinese MedicineAbstract The present study aimed to investigate the role of the PI3K/Akt signaling pathway in scleral remodeling in the development of negative lens-induced myopia (LIM). 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-β1), 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-β1, TIMP2, and COLI. Results reveal that the disturbed PI3K/AKT signaling plays a role in scleral remodeling in the experimental myopia through orchestrating apoptosis.https://doi.org/10.1038/s41598-025-97643-7Experimental myopiaPI3K/Akt signaling pathwayTGF-β1CollagenScleral remodeling
spellingShingle Xiaomeng Li
Xiaojing Liu
Yingxin Yu
Tuling Li
Lijie Guo
Guili Hu
Huixia Wei
Zhaohui Yang
Jinpeng Liu
Yixian Hao
Ruixue Zhang
Qiuxin Wu
Xuan Liao
Dadong Guo
Hongsheng Bi
Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia
Scientific Reports
Experimental myopia
PI3K/Akt signaling pathway
TGF-β1
Collagen
Scleral remodeling
title Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia
title_full Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia
title_fullStr Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia
title_full_unstemmed Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia
title_short Covariation of scleral remodeling and PI3K/Akt signaling pathway in experimental myopia
title_sort covariation of scleral remodeling and pi3k akt signaling pathway in experimental myopia
topic Experimental myopia
PI3K/Akt signaling pathway
TGF-β1
Collagen
Scleral remodeling
url https://doi.org/10.1038/s41598-025-97643-7
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