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Role of Integrin β1 subunit Loss in Conjunctivochalasis: A Mechanistic Study of MMP-Mediated Extracellular Matrix
Nixia Tao1, Binxin Wang1, Xueqing Kong1
1Department of Ophthalmology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.
Abstract:
This study investigated the role of Integrin β1 subunit in conjunctivochalasis (CCH) using clinical specimens, shRNA-mediated in vitro models, and an MMP-3-induced in vivo rabbit model. Clinical and rabbit CCH tissues exhibited severe stromal edema along with collagen and elastic fiber degradation. In CCH-derived human conjunctival fibroblasts, Integrin β1 subunit and Collagen I were significantly downregulated, while MMP-2 and MMP-9 were upregulated. Mechanistically, shRNA-mediated knockdown of Integrin β1 subunit directly triggered a sharp increase in MMP-2 and MMP-9 expression, suppressed Collagen I synthesis, and severely impaired fibroblast proliferation and migration. Furthermore, the MMP-3-induced rabbit model successfully recapitulated hallmark clinical features of CCH, including loose conjunctival folds, tissue thinning on anterior segment OCT, all of which strongly correlated with the localized downregulation of Integrin β1 subunit in rabbit conjunctival stroma. In conclusion, Integrin β1 subunit deficiency is a pivotal driver of CCH pathogenesis. Its loss accelerates extracellular matrix degradation via aberrant MMP-2/9 activation and induces fibroblast dysfunction, leading to the tissue thinning and laxity characteristic of CCH.
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