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Article

The Function of Transforming Growth Factor 2 in Facilitating Inflammasome Activation to Enhance the Development of Myopia via Complement System

1
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan
2
School of Chinese Medicine, China Medical University, Taichung 406040, Taiwan
3
Department of Chemistry, National Central University, Taoyuan 320317, Taiwan
4
Ph.D. Program for Health Science and Industry, China Medical University, Taichung 406040, Taiwan
5
Department of Food Nutrition and Health Biotechnology, Asia University, Taichung 413305, Taiwan
6
Division of Chinese Medicine, Asia University Hospital, Taichung 413505, Taiwan
7
School of Medicine, China Medical University, Taichung 406040, Taiwan
8
Eye Center, China Medical University Hospital, Taichung 404327, Taiwan
9
Department of Emergency Medicine, Taichung Tzu Chi Hospital, Taichung 42743, Taiwan
10
Department of Medical Laboratory Science and Biotechnology, Asia University, Taichung 41354, Taiwan
11
Department of Beauty Science, National Taichung University of Science and Technology, Taichung 403027, Taiwan
12
Department of Obstetrics and Gynecology, China Medical University Hospital, Taichung 40402, Taiwan
*
Authors to whom correspondence should be addressed.
Cells 2025, 14(16), 1295; https://doi.org/10.3390/cells14161295
Submission received: 16 May 2025 / Revised: 15 August 2025 / Accepted: 19 August 2025 / Published: 20 August 2025

Abstract

Myopia is one of the major public health conditions with significant complications. This study investigates the role of transforming growth factor (TGF)-β2, 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-β2 exacerbated myopia by upregulating complement components C3 and C5, suppressing CD55, and activating inflammasome pathways through nuclear factor (NF)-κB 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)-1β and NLR family pyrin domain containing 3 (NLRP3), as confirmed by real-time quantitative PCR and immunofluorescence analyses. Conversely, silencing CD55 intensified TGF-β2-induced effects, further promoting axial elongation and inflammation. These findings highlight the critical role of CD55 in modulating TGF-β2-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.
Keywords: myopia; TGF-β2; complement system; CD55; inflammasome; NF-κB; gene therapy myopia; TGF-β2; complement system; CD55; inflammasome; NF-κB; gene therapy

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MDPI and ACS Style

Lin, S.-C.; Hsu, Y.-A.; Lin, C.-F.; Chen, C.-S.; Tien, P.-T.; Wang, Y.-C.; Chang, C.-Y.; Lin, E.-S.; Chen, J.J.-Y.; Wu, M.-Y.; et al. The Function of Transforming Growth Factor 2 in Facilitating Inflammasome Activation to Enhance the Development of Myopia via Complement System. Cells 2025, 14, 1295. https://doi.org/10.3390/cells14161295

AMA Style

Lin S-C, Hsu Y-A, Lin C-F, Chen C-S, Tien P-T, Wang Y-C, Chang C-Y, Lin E-S, Chen JJ-Y, Wu M-Y, et al. The Function of Transforming Growth Factor 2 in Facilitating Inflammasome Activation to Enhance the Development of Myopia via Complement System. Cells. 2025; 14(16):1295. https://doi.org/10.3390/cells14161295

Chicago/Turabian Style

Lin, Sheng-Chun, Yu-An Hsu, Chi-Fong Lin, Chih-Sheng Chen, Peng-Tai Tien, Yao-Chien Wang, Ching-Yao Chang, En-Shyh Lin, Jamie Jiin-Yi Chen, Ming-Yen Wu, and et al. 2025. "The Function of Transforming Growth Factor 2 in Facilitating Inflammasome Activation to Enhance the Development of Myopia via Complement System" Cells 14, no. 16: 1295. https://doi.org/10.3390/cells14161295

APA Style

Lin, S.-C., Hsu, Y.-A., Lin, C.-F., Chen, C.-S., Tien, P.-T., Wang, Y.-C., Chang, C.-Y., Lin, E.-S., Chen, J. J.-Y., Wu, M.-Y., Lin, H.-J., & Wan, L. (2025). The Function of Transforming Growth Factor 2 in Facilitating Inflammasome Activation to Enhance the Development of Myopia via Complement System. Cells, 14(16), 1295. https://doi.org/10.3390/cells14161295

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