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Integrin-Mediated Matrix Attachment and Vitreous Contraction of Cultured Human Retinal Pigment Epithelial Cells

Integrin引起視網膜色素上皮細胞對間質之附著及玻璃體收縮

摘要


增殖性玻璃體視網膜病變是造成視網膜剝離手術失敗的最大原因,其致病機轉至今仍未十分明瞭。細胞附著因子integrin是位於細胞表面對於細胞外間質成分的受器,integrin可能參與增殖性玻璃體視網膜病變之致病機轉。本實驗之目的即欲以培養之人眼視網膜色素上皮細胞為對象,探討integrin在細胞附著及引起玻璃體收縮上所扮演之角色。 我們以間接免疫螢光染色法及流動細胞計數儀來顯示及定量integrin在視網膜色素上皮細胞的表現,以細胞附著實驗及玻璃體收縮實驗來證實integrin的功能。實驗結果顯示培養之人眼視網膜色素上皮細胞可以表現collagen,fibronectin,vitronectin及laminin等細胞外間質成分之受器。視網膜色素上皮細胞即利用此受器附著於細胞外間質。此附著作用能被抗integrin之單株抗體所阻斷。視網膜色素上皮細胞能利用integrin使玻璃體收縮。此作用需要有二價陽離子之參與。此外細胞間素亦可加強此收縮作用。 綜合實驗之結果,我們發現培養之人眼視網膜色素上皮細胞可以表現integrin,細胞即利用這些integrin附著於細胞外間質並且使玻璃體收縮。這種機制在增殖性玻璃體視網膜病變的致病機轉上可能扮演一重要的角色。

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並列摘要


Background: The pathogenesis of proliferative vitreoretinopathy (PVR) is not fully understood. Integrins, a group of cell surface extracellular matrix (ECM) receptors, are thought to play an active role. Integrin-mediated ECM adhesion and vitreous contraction of human retinal pigment epithelial (RPE) cells were investigated in this study. Methods: Indirect immunofluorescent stain and flow cytometry were used to demonstrate and quantify the expression of integrins on cultured human RPE cells. The functional expression of integrins on RPE cells was evaluated by cell adhesion assay and bovine vitreous contraction assay with specific monoclonal anti-integrin subunit antibodies. Results: Cultured human RPE cells expressed collagen, fibronectin, vitronectin, and laminin receptors on the cell membranes. RPE cells used these integrins to attach to ECM proteins, and the attachment was blocked by integrin-specific monoclonal antibodies. In the vitreous gel model, RPE cells showed divalent-cation dependent vitreous contraction via α2β1 and α3β1 intrgrins. Cytokines enhanced the integrin-mediated vitreous contraction. Conclusion: Human RPE cells express β1 family and α(subscript v)β3 integrins that mediated ECM attachment and vitreous contraction. These integrins on the RPE cells may play an important role in the pathogenesis of PVR.

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