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This study investigates the role of transforming growth factor (TGF)-\u03b22, complement activation, and inflammasome pathways in myopia progression using a Brown Norway rat model. Myopia was induced, and complement regulation was manipulated using gene therapy via adeno-associated virus (AAV) vectors delivering CD55 or CD55 siRNA. Results showed that TGF-\u03b22 exacerbated myopia by upregulating complement components C3 and C5, suppressing CD55, and activating inflammasome pathways through nuclear factor (NF)-\u03baB signaling, leading to axial elongation and increased refractive errors. Overexpression of CD55 via AAV gene therapy effectively counteracted these effects, reducing axial length elongation and inflammation by suppressing inflammasome markers interleukin (IL)-1\u03b2 and NLR family pyrin domain containing 3 (NLRP3), as confirmed by real-time quantitative PCR and immunofluorescence analyses. Conversely, silencing CD55 intensified TGF-\u03b22-induced effects, further promoting axial elongation and inflammation. These findings highlight the critical role of CD55 in modulating TGF-\u03b22-driven complement and inflammasome activation during myopia progression. The study suggests that gene therapy targeting CD55 could serve as a novel therapeutic strategy to mitigate myopia and related inflammatory processes, offering a promising avenue for managing this significant public health challenge.<\/jats:p>","DOI":"10.3390\/cells14161295","type":"journal-article","created":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T13:18:14Z","timestamp":1755695894000},"page":"1295","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Function of Transforming Growth Factor 2 in Facilitating Inflammasome Activation to Enhance the Development of Myopia via Complement System"],"prefix":"10.3390","volume":"14","author":[{"given":"Sheng-Chun","family":"Lin","sequence":"first","affiliation":[{"name":"Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan"},{"name":"School of Chinese Medicine, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-An","family":"Hsu","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Department of Chemistry, National Central University, Taoyuan 320317, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-9191","authenticated-orcid":false,"given":"Chi-Fong","family":"Lin","sequence":"additional","affiliation":[{"name":"Ph.D. Program for Health Science and Industry, China Medical University, Taichung 406040, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 413305, Taiwan"},{"name":"Division of Chinese Medicine, Asia University Hospital, Taichung 413505, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9099-3151","authenticated-orcid":false,"given":"Peng-Tai","family":"Tien","sequence":"additional","affiliation":[{"name":"School of Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao-Chien","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Taichung Tzu Chi Hospital, Taichung 42743, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Yao","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"En-Shyh","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Beauty Science, National Taichung University of Science and Technology, Taichung 403027, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jamie Jiin-Yi","family":"Chen","sequence":"additional","affiliation":[{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Yen","family":"Wu","sequence":"additional","affiliation":[{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Eye Center, China Medical University Hospital, Taichung 404327, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-3232","authenticated-orcid":false,"given":"Lei","family":"Wan","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 406040, Taiwan"},{"name":"Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan"},{"name":"Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 40402, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1016\/S0140-6736(12)60272-4","article-title":"Myopia","volume":"379","author":"Morgan","year":"2012","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.2471\/BLT.07.041210","article-title":"Global Magnitude of Visual Impairment Caused by Uncorrected Refractive Errors in 2004","volume":"86","author":"Resnikoff","year":"2008","journal-title":"Bull. 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