A potential pathophysiologic role for alpha 2 beta 1 integrin in human eye diseases involving vitreoretinal traction.
Cell-mediated contraction of tissues containing fibrillar collagens can lead to organ compromise and loss of function. The same process that is biologically advantageous during the contraction phase of wound healing can be subverted in diseases such as hepatic cirrhosis, pulmonary fibrosis, and scleroderma, although the cellular and molecular mechanism of matrix tissue contraction is difficult to study in such chronic diseases. However, certain human eye diseases that result in tractional detachment of the retina and loss of vision are characterized by acute cell-mediated contraction of collagenous tissue in the vitreous cavity. In this study, we demonstrate that human cells can contract vitreous, a complex biological gel containing type II collagen, in vitro. This cell-mediated contraction can be blocked by antibodies and peptides that antagonize the function of alpha 2 beta 1 integrin, and the potential for contraction can be conferred upon noncontracting cells by stable transfection of cells with alpha 2 cDNA. We also show that this contractile process, if focally resisted, can result in remodeling vitreous from a gel to a structure that resembles a planar membrane, and that substantial isometric forces can be measured across this tissue. We propose that in diseases such as proliferative diabetic retinopathy and proliferative vitreoretinopathy, alpha 2 beta 1 integrin-mediated contraction of the vitreous and tension at the site of vitreoretinal attachments contribute to the terminal event of tractional retinal detachment. By extension, we propose that alpha 2 beta 1 integrin is a centrally important molecule in human diseases characterized by remodeling and contraction of collagenous tissue (i.e., fibrocontractive diseases).
Kupper
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Division of Dermatology, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Ferguson
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D000906:Antibodies / Q000494:pharmacology; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D003094:Collagen / Q000502:physiology; D005128:Eye Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D010857:Pigment Epithelium of Eye / Q000473:pathology / Q000503:physiopathology; D012160:Retina / Q000503:physiopathology*; D014162:Transfection; D014822:Vitreous Body / Q000503:physiopathology*
D000906:Antibodies; D016023:Integrins; D003094:Collagen