Abstract
Objective: To determine the effects of age and topographic location on gene expression in human neural retina. Methods: Macular and peripheral neural retina RNA was isolated from human donor eyes for DNA microarray and quantitative RT-PCR analyses. Results: Total RNA integrity from human donors was preserved. Hierarchical clustering analysis demonstrates that the gene expression profiles of young, old, macula, and peripheral retina cluster into four distinct groups. Genes which are highly expressed in macular, peripheral, young, or old retina were identified, including inhibitors of Wnt Signaling Pathway (DKK1, FZD10, and SFRP2) which are preferably expressed in the periphery. Conclusion: The transcriptome of the human retina is affected by age and topographic location. Wnt pathway inhibitors in the periphery may maintain peripheral retinal cells in an undifferentiated state. Understanding the effects of age and topographic location on gene expression may lead to the development of new therapeutic interventions for age-related eye diseases.
Highlights
In the normal human eye the neural retina develops from mesoderm and forms a multilaminated structure with highly specialized functions for light detection and signal processing (Ye et al, 1999)
Examples of age-dependent diseases of the retina include glaucoma and age-related macular degeneration (AMD), in which structural changes leading to visual loss develop in ganglion cells or outer retina, RPE, and choriocapillaris (Nag et al, 2006)
A systematic comparison of the gene expression profiles of young vs. older neural retina is important, as analysis of the retinal transcriptome may allow us to define a role for some genes in either initiating or responding to the cellular changes that occur in age-dependent diseases such as AMD
Summary
In the normal human eye the neural retina develops from mesoderm and forms a multilaminated structure with highly specialized functions for light detection and signal processing (Ye et al, 1999). Examples of age-dependent diseases of the retina include glaucoma and age-related macular degeneration (AMD), in which structural changes leading to visual loss develop in ganglion cells or outer retina, RPE, and choriocapillaris (Nag et al, 2006). Cellular changes that occur in AMD include atrophy of the RPE, choriocapillaris, and outer retina in non-exudative AMD as well as the development of choroidal or intraretinal neovascularization in exudative AMD (Chader, 2002). A systematic comparison of the gene expression profiles of young vs older neural retina is important, as analysis of the retinal transcriptome may allow us to define a role for some genes in either initiating or responding to the cellular changes that occur in age-dependent diseases such as AMD. Topographic location may affect gene expression profiling, since some diseases such as AMD affect the macula and periphery differently (van Soest et al, 2007)
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