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TGF-β/RhoA/ROCK Signaling Activation Orchestrates Ciliary Body EMT and Fibrosis in Myopia
Xuewei Yin1,2,3, Yixian Hao2, Zhongyu Ma1
1School of Ophthalmology and Optometry, Shandong University of Traditional Chinese Medicine, 250002 Jinan, Shandong, China.
Frontiers in Bioscience (Landmark Edition)
|January 29, 2026
Summary
The transforming growth factor-β/Ras homolog family member A/Rho-associated protein kinase pathway promotes ciliary body fibrosis in myopia. Inhibiting Rho-associated protein kinase alleviates epithelial-mesenchymal transition and fibrosis, offering new insights into myopia development.
Area of Science:
- Ophthalmology
- Molecular Biology
- Pathology
Background:
- The transforming growth factor (TGF)-β/Ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway is implicated in fibrotic changes in ocular diseases.
- Dysregulation of this pathway may contribute to epithelial-mesenchymal transition (EMT) and fibrosis in the ciliary body.
Purpose of the Study:
- To investigate the role of the TGF-β/RhoA/ROCK pathway in EMT and fibrosis within the ciliary body of guinea pigs with lens-induced myopia (LIM).
Main Methods:
- Established a lens-induced myopia model in guinea pigs.
- Assessed refraction, axial length, and ciliary body alterations using qPCR, western blot, PCR array, histology, and biomechanical analyses.
- Utilized Ingenuity Pathway Analysis to explore upstream mechanisms and Y-27632 (a ROCK inhibitor) for functional experiments.
Main Results:
- Myopic guinea pigs showed increased refraction and axial length, with elevated TGF-β1, RhoA, ROCK1, ROCK2, α-SMA, and MMP1 levels in the ciliary body.
- Functional changes preceded EMT transcription factor level changes in early myopia.
- Myopic ciliary bodies exhibited increased Ca2+ inflow, higher Young's modulus, reduced elasticity, and aggravated fibrosis, which were alleviated by ROCK inhibition.
Conclusions:
- Activation of the TGF-β/RhoA/ROCK pathway induces EMT, promotes Ca2+ inflow, and reduces ciliary body elasticity in myopia, leading to fibrosis and dysfunction.
- This pathway offers a novel perspective on the pathological mechanisms of ciliary body fibrosis in myopia development.
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