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T. Adewoyin, E. Fletcher, S. Sivaprasad, V. L. Calder, K. Gregory-Evans, V. Chong; Serum Matrix Metalloproteinase Profile in Neovascular Age Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2010;51(13):4110.
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Age related macular degeneration (AMD) is a complex disorder with a multifactorial aetiology. Structural changes in Bruch’s membrane occur in AMD. Extracellular matrix dysregulation, due to aberrant activity of matrix metalloproteinases (MMPs) and their inhibitors, might play a role in the pathogenesis of AMD. HTRA1 is associated with AMD. The exact mechanism remains unknown. As it was suggested that HTRA1 might be a serine proteinases, we would like to assess whether HTRA1 "at risk" alleles would alter MMPs levels.
Two hundred and forty eight Caucasian patients were recruited. Classification of the cohort into controls, drusen and neovascular AMD was made by biomicroscopy and fundal photography. Genotyping of 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 microarray .
MMP 9 and MMP10 was significantly raised in patients positive for the risk allele (p<0.02, p<0.09 respectively)There was also a significant difference in MMP 1, 8, TIMP2 & 4 levels in drusen (p=0.016, p=0.029, p=0.002, p=0.034 and AMD groups (p=0.004,p= 0.010, p<0.00001,p=0.002 ,p=0.04) compared to control.
AMD pathogenesis is complex and not fully elucidated at present. HtrA1 has been shown to confer an increased risk of AMD, and influences the expression of metalloproteinases. Identification of biomarkers that vary in disease states can help with prediction and prognosis as well as developing novel therapy.
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