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A.I. Jobling, R. Metlapally, N.A. McBrien; Identification of Integrin Receptors within the Mammalian Sclera and their Possible Role in Myopia . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2799.
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Purpose: The integrin family of cell surface receptors have critical roles in cell-cell, cell-extracellular matrix (ECM) and mechanical stress signaling. Despite the mammalian sclera exhibiting extensive ECM alterations during abnormal eye growth, data on integrin expression are limited. This study assessed integrin expression within the tree shrew sclera using a gene array and targeted PCR approach. It also examined integrin expression during myopia induction. Methods: Human clones were used in a custom array which included almost all of the known integrin subunits (17/18α and 8/8ß). Tree shrew total RNA was isolated from posterior scleral tissue, cDNA was amplified using universal primers and a Virtual Northern was performed. The α1, α2 and ß1 integrin subunits were targeted since they are the major collagen-binding receptors. Specific primers were designed to areas of high inter-species homology. Expression was assessed in scleral cDNA and in a primary tree shrew scleral fibroblast cell line. Integrin expression was also examined after 1 and 5 days myopia induction using real-time PCR. Results: Integrin subunits were detected in the tree shrew sclera. Of particular interest were the α1, α2 and ß1 subunits, whose expression was confirmed in both scleral tissue and in a primary tree shrew scleral fibroblast cell line. Tree shrew sequence data showed the integrins to have a high homology to their human counterparts (>85%). Induction of myopia resulted in time dependent changes in the expression of these integrin subunits. After only 1 day, decreases were observed in ß1 and α2-integrins (31%, 17% respectively). Following 5 days myopia induction, ß1-integrin levels had almost returned to that of the control eye, whilst the α1 subunit remained suppressed (20%). Conclusion: Integrin subunits were detected in the tree shrew sclera. Presumably integrins are critical to normal cell-ECM communication and stress signaling in the sclera. The collagen binding integrin subunits, α1, α2 and ß1, are specifically regulated during myopia induction. These early changes may result in the later alterations in scleral ECM and biomechanical properties.
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