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CP Dugan, G Choi, ME Fini, JA West-Mays; Evidence that Matrix Metalloproteinases Participate in Lens Development and Cataractogenesis . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3549.
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Purpose:Matrix Metalloproteinases (MMPs) are a family of enzymes known to participate in numerous remodeling events during development as well as in disease. In the eye, important roles for MMPs have been shown in corneal wound healing, retinal disease, and glaucoma. Much less is known about the function of MMPs in the normal and cataractous lens. We investigated the role of gelatinase A (MMP-2) and gelatinase B (MMP-9) in the normal and cataractous lens. Methods:Expression of MMP-2 and MMP-9 was determined in the normal rat and mouse lens using immunohistochemistry, as well as in rat lenses following TGFß induced subcapsular cataract formation. MMP-9 promoter activity was determined using a previously established gelB-LacZ mouse model. Histological evaluation of lenses from MMP-2 and MMP-9 knockout mice was also carried out. Results:MMP-2 was not constitutively expressed in the adult mouse and rat lens. In contrast, MMP-9 promoter activity was detected in the lens, specifically in the anterior lens epithelium. In the TGFß treated rat lens an induction in MMP-2 expression was observed and this was correlated with the location of the subcapsular cataracts. MMP-2 knockout mouse lenses appeared similar to wild-type lenses. Lenses from adult MMP-9 null mice appeared relatively normal, with the exception that the lens capsule was thickened as compared to wild-type lenses. Conclusion:These data support the hypothesis that MMP-9 is required for normal morphogenesis of the lens and MMP-2 expression in the adult lens is associated with a pathological (cataract) phenotype.
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