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N. Yeremenko, S. van Soest, G.M. J. de Wit, A. Essing, W. Kamphuis, P.T. V. M. de Jong, A.A. B. Bergen; Photoreceptor Gene Expression Alterations in Aging and Early Stage of Age Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2006;47(13):4746.
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© ARVO (1962-2015); The Authors (2016-present)
Age related macular degeneration (AMD) is a heterogeneous group of disorders characterized by photoreceptor degeneration and atrophy of the retinal pigment epithelium in the central retina. We aim to identify photoreceptor gene expression alterations associated with aging and with early stage of AMD in order to obtain insight into molecular pathways underlying these processes.
The early stage of AMD was defined based on the presence of a large number of drusen in the macula area. The outer photoreceptor layer was isolated by laser microdissection. Gene expression patterns in photoreceptor cells were characterized from 5 young donors, 8 old unaffected donors and 8 old donors with early stage of AMD using 44K Whole Genome Human microarrays (Agilent). The expression data were normalized and analyzed using the R software package LIMMA. Differential expression was assessed using linear models and empirical Bayes moderated F statistics. Quantitative real–time RT–PCR (QPCR) was applied to validate microarray results on the same set of eyes used for array experiments.
In photoreceptors from early stage of AMD 1534 and 1438 genes were up and down regulated compared with old healthy photoreceptors (p<0.001). This number was slightly reduced in young versus old group and comprised 971 genes for up and 707 for down regulation. Gene expression profile was sorted according to metabolic pathways. Based on the specificity of data obtained potential targets were chosen for further study by means of immunocytochemistry.
Together with some genes known to contribute to the onset of AMD many novel genes were identified. Results obtained highlight the complexity of the molecular processes associated with AMD. Identification of cell specific response in healthy and AMD–affected retinas is a powerful tool for the discovery of AMD related genes and pathways. Some of the genes identified in this research are candidates for further studies aimed to elucidate their potential role in AMD pathogenesis.
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