Lin Sheng-Chun, Hsu Yu-An, Lin Chi-Fong, Chen Chih-Sheng, Tien Peng-Tai, Wang Yao-Chien, Chang Ching-Yao, Lin En-Shyh, Chen Jamie Jiin-Yi, Wu Ming-Yen, Lin Hui-Ju, Wan Lei
Graduate Institute of Biomedical Sciences, China Medical University, Taichung 406040, Taiwan.
School of Chinese Medicine, China Medical University, Taichung 406040, Taiwan.
Cells. 2025 Aug 20;14(16):1295. doi: 10.3390/cells14161295.
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.
近视是一种伴有严重并发症的主要公共卫生疾病。本研究使用棕色挪威大鼠模型，探讨转化生长因子（TGF）-β2、补体激活和炎性小体途径在近视进展中的作用。诱导近视，并通过腺相关病毒（AAV）载体递送CD55或CD55小干扰RNA（siRNA），利用基因疗法操纵补体调节。结果显示，TGF-β2通过上调补体成分C3和C5、抑制CD55以及通过核因子（NF）-κB信号激活炎性小体途径来加重近视，导致眼轴伸长和屈光不正增加。通过AAV基因疗法过表达CD55可有效抵消这些影响，通过抑制炎性小体标志物白细胞介素（IL）-1β和含NLR家族pyrin结构域3（NLRP3）来减少眼轴长度伸长和炎症，实时定量PCR和免疫荧光分析证实了这一点。相反，沉默CD55会增强TGF-β2诱导的效应，进一步促进眼轴伸长和炎症。这些发现突出了CD55在近视进展过程中调节TGF-β2驱动的补体和炎性小体激活中的关键作用。该研究表明，靶向CD55的基因疗法可作为一种减轻近视及相关炎症过程的新型治疗策略，为应对这一重大公共卫生挑战提供了一条有前景的途径。
