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Characterization of Anatomical, Macromolecular, and Gene Expression Changes in the Retinal and Retinal Pigmented Epithelium of the nm3342 Mouse: A Potential Model of Serous Retinal Detachment

ABSTRACT: To characterize gene expression changes in mice following serous retinal detachments, we employed whole genome microarray expression profiling as a tool to identify genes with the potential effects on the neural retina as well as retinal pigmented epithelium. Total RNA was harvested from nm3342 (mutant) and age-matched wild-type (C57Bl/6J) mice at P30 or P365 for examination using microarray analysis.

ORGANISM(S): Mus musculus

PROVIDER: GSE68961 | GEO | 2015/05/16

SECONDARY ACCESSION(S): PRJNA284167

REPOSITORIES: GEO

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Characterization of Anatomical, Macromolecular, and Gene Expression Changes in the Retinal and Retinal Pigmented Epithelium of the nm3342 Mouse: A Potential Model of Serous Retinal Detachment

Project description:To characterize gene expression changes in mice following serous retinal detachments, we employed whole genome microarray expression profiling as a tool to identify genes with the potential effects on the neural retina as well as retinal pigmented epithelium. Total RNA was harvested from nm3342 (mutant) and age-matched wild-type (C57Bl/6J) mice at P30 or P365 for examination using microarray analysis. Retinas and retinal pigmented epithelium was harvested from both age-matched mutant and wild-type mice.

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Anatomical and Gene Expression Changes in the Retinal Pigmented Epithelium Atrophy 1 (rpea1) Mouse: A Potential Model of Serous Retinal Detachment.

Project description:The purpose of this study was to examine the rpea1 mouse whose retina spontaneously detaches from the underlying RPE as a potential model for studying the cellular effects of serous retinal detachment (SRD).Optical coherence tomography (OCT) was performed immediately prior to euthanasia; retinal tissue was subsequently prepared for Western blotting, microarray analysis, immunocytochemistry, and light and electron microscopy (LM, EM).By postnatal day (P) 30, OCT, LM, and EM revealed the presence of small shallow detachments that increased in number and size over time. By P60 in regions of detachment, there was a dramatic loss of PNA binding around cones in the interphotoreceptor matrix and a concomitant increase in labeling of the outer nuclear layer and rod synaptic terminals. Retinal pigment epithelium wholemounts revealed a patchy loss in immunolabeling for both ezrin and aquaporin 1. Anti-ezrin labeling was lost from small regions of the RPE apical surface underlying detachments at P30. Labeling for tight-junction proteins provided a regular array of profiles outlining the periphery of RPE cells in wild-type tissue, however, this pattern was disrupted in the mutant as early as P30. Microarray analysis revealed a broad range of changes in genes involved in metabolism, signaling, cell polarity, and tight-junction organization.These data indicate changes in this mutant mouse that may provide clues to the underlying mechanisms of SRD in humans. Importantly, these changes include the production of multiple spontaneous detachments without the presence of a retinal tear or significant degeneration of outer segments, changes in the expression of proteins involved in adhesion and fluid transport, and a disrupted organization of RPE tight junctions that may contribute to the formation of focal detachments.

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Characterization of Stem-cell derived Retinal Pigmented Epithelium (RPE)

Project description:To assess the geome-wide similarities between primary fetal retinal pigmented epithelium (RPE) and stem-cell derived RPE, we performed whole genome microarray expression on primary RPE and both embryonic stem cell (ESC) derived RPE and induced pluripotent stem cell (iPSC) derived RPE. We found ES-derived RPE better resembles fetal RPE than iPS-derived RPE.

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Project description:In mammalian albinism, disrupted melanogenesis in the retinal pigment epithelium (RPE) is associated with fewer retinal ganglion cells (RGCs) projecting ipsilaterally to the brain, resulting in numerous abnormalities in the retina and visual pathway, especially binocular vision. To further understand the molecular link between disrupted RPE and a reduced ipsilateral RGC projection in albinism, we compared gene expression in the embryonic albino and pigmented mouse RPE.

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Characterization of Stem-cell derived Retinal Pigmented Epithelium (RPE)

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Gene Expression Analysis of Zebrafish Melanocytes, Iridophores, and Retinal Pigmented Epithelium Reveals Indicators of Biological Function and Developmental Origin

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Project description:Aging is the main risk factor for age-related macular degeneration (AMD), a retinal neurodegenerative syndrome that leads to irreversible blindness, particularly in people over 60 years old. Retinal pigmented epithelium (RPE) atrophy is an AMD hallmark that often precedes photoreceptor loss. Genome-wide chromatin accessibility, DNA methylation, and gene expression studies of AMD and control RPE demonstrate epigenomic/transcriptomic changes occur during AMD onset and progression. However, mechanisms by which molecular alterations of normal aging impair RPE function and contribute to AMD pathogenesis are unclear. Here, we specifically interrogate the RPE translatome with advanced age and across sexes in a novel mouse model. We find differential age- and sex- associated transcript expression with overrepresentation of pathways related to inflammation in the RPE. Concordant with impaired RPE function, the phenotypic changes in the aged translatome suggest that aged RPE becomes immunologically active, in both males and females, with some sex-specific signatures, which supports the need for sex representation for in vivo studies.

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