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Temilade Adewoyin, Emily Fletcher, Virginia L. Calder, Kevin Gregory-Evans, Sobha Sivaprasad, Victor Chong; The Association Of MMP/TIMP Ratios In Neovascular AMD. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2341.
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© ARVO (1962-2015); The Authors (2016-present)
Age related macular degeneration is a complex disorder with a multifactorial aetiology. Pathological changes in neovascular AMD are in part attributable to structural changes in Bruch’s membrane. Extracellular matrix dysregulation, due to aberrant activity of matrix metalloproteinases and their inhibitors plays a role in this pathology. There are three key endogenous tissue inhibitors , TIMP1,2 and 4 which act against all active forms of metalloproteinases. The fine balance of MMP to TIMP determines the microenvironment of the cells, thus an imbalance can result in a pathological process. A polymorphism in the HTRA1 gene is associated with an increased risk of nAMD. Expression of metalloproteinases is known to be influenced by this gene. This study was conducted to ascertain if the MMP/TIMP profile in patients with neovascular AMD differed compared to controls and with regard their allelic variation of HTRA1.
248 Caucasian patients were recruited. Classification of the cohort into controls, drusen and neovascular age related macular degeneration was made by biomicroscopy and fundal photography. Genotyping using the single nucleotide polymorphism for HtrA1 rs11200638 was also performed. Serum samples were analysed to determine the MMP profile ( 7 MMP’s, 3 TIMPS’s) using a human MMP protein array. The ratio of each MMP relative to TIMP1, 2 and 4 was determined.
The ratios of MMP1/TIMP1, MMP2/TIMP1, MMP8/TIMP1, MMP13/TIMP1, MMP8/TIMP2 and MMP9/TIMP2 were found to be significantly lowered in patients with AMD (p=0.002, p=0.022, p=0.007,p=0.003,p=0.005,p=0.06)) compared to controls. Ratios of MMP8/TIMP4, MMP9/TIMP4, were significantly elevated compared to controls in the AMD cohort. With regard to genotype MMP9/TIMP2, MMP10/TIMP2, MMP2/TIMP4, MMP9/TIMP4, MMP10/TIMP4 ratios showed a significant increase with regard to the risk allele (p=0.018, p=0.013, p=0.01, p=0.02, p=0.003)
AMD pathogenesis is complex and not fully elucidated at present. Metalloproteinases are a ubiquitous group of proteins with many biochemical and cellular interactions and have been shown to have an important role in the pathological process that occurs in neovascular AMD. Identification of biomarkers that vary in disease states can help with prediction and prognosis.
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