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L. V. Del Priore, H. Cai; Differential Spatial and Temporal Expression of Wnt Signaling Pathway Genes in Human Retina. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2955.
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© ARVO (1962-2015); The Authors (2016-present)
The Wnt signaling pathway is involved in retinal development and may play a role in the pathogenesis of age-related macular degeneration (AMD). Prior studies suggest that this pathway is involved in embryonic stem differentiation into retinal progenitor cells. The purpose of this study is to determine the expression pattern of Wnt signaling pathway genes in peripheral and macular neural retina in young and older human eyes, and discuss the implications of these findings in the pathology of age-related eye disease.
Macular and peripheral neural retina RNA were isolated from twelve (12) human eyebank donors (young = 18-43 years; old = 72-79 years) within 48 hours of death. The Affymetrix human genome chip U133v2 was used for DNA microarray studies. Genes were identified as Wnt signaling pathway-related using the Affymetrix’s NetAffy and Gene Ontology molecular and biological function online gene annotation tools. Genesifter and several other microarray analysis software systems were used to perform clustering analysis.
Hierarchical clustering analysis demonstrates that the global gene expression profiles of young, old, macular and peripheral retina cluster into four distinct groups. All of the 132 Wnt-related genes are present in each of these four subgroups, but there is significant variation in the expression level of Wnt-related genes as a function of age and topographic location. For example, the expression level of FZD8 is > 2 fold higher in young versus older macula, whereas catenin, a cadherin-associated protein, is expressed 2-fold higher in young versus older peripheral retina. Wnt signaling inhibitors (DKK1, FZD10 and SFRP2) are highly expressed in the periphery compared to macular retina (>4.9 fold).
The expression profiles of genes related to Wnt signaling pathway in human retina are affected by age and topographic location. Expression of Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Our data suggest that activation of Wnt signaling in peripheral retina and ciliary marginal zone may provide a therapeutic strategy for in vitro expansion or in vivo activation of cells in the retinal periphery.
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