Transcriptional mapping of the macaque retina and RPE-choroid reveals conserved inter-tissue transcription drivers and signaling pathways
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ABSTRACT:
ORGANISM(S): Macaca mulatta
PROVIDER: GSE194285 | GEO | 2022/01/24
REPOSITORIES: GEO
Similar Datasets
Project description:The macula is an essential region of the retina responsible for visual acuity. Abnormalities in development of the fovea at the center of the macula lead to severe diseases. To identify macula-specific differentially expressed genes in maturing stage of macular development, we compared the gene expression profiles of the macular and peripheral region of the pediatric retina.
2023-03-31 | GSE144300 | GEO
Project description:<p>Proper spatial differentiation of retinal cell types is necessary for normal human vision. Many retinal diseases, such as Best disease and male germ cell associated kinase (MAK)-associated retinitis pigmentosa, preferentially affect distinct topographic regions of the retina. While much is known about the distribution of cell types in the retina, the distribution of molecular components across the posterior pole of the eye has not been well-studied. To investigate regional difference in molecular composition of ocular tissues, we assessed differential gene expression across the temporal, macular, and nasal retina and retinal pigment epithelium (RPE)/choroid of human eyes using RNA-Seq. RNA from temporal, macular, and nasal retina and RPE/choroid from four human donor eyes was extracted, poly-A selected, fragmented, and sequenced as 100 bp read pairs. Digital read files were mapped to the human genome and analyzed for differential expression using the Tuxedo software suite. Retina and RPE/choroid samples were clearly distinguishable at the transcriptome level. Numerous transcription factors were differentially expressed between regions of the retina and RPE/choroid. Photoreceptor-specific genes were enriched in the peripheral samples, while ganglion cell and amacrine cell genes were enriched in the macula. Within the RPE/choroid, RPE-specific genes were upregulated at the periphery while endothelium associated genes were upregulated in the macula. Consistent with previous studies, BEST1 expression was lower in macular than extramacular regions. The MAK gene was expressed at lower levels in macula than in extramacular regions, but did not exhibit a significant difference between nasal and temporal retina. The regional molecular distinction is greatest between macula and periphery and decreases between different peripheral regions within a tissue. Datasets such as these can be used to prioritize candidate genes for possible involvement in retinal diseases with regional phenotypes. </p> <p>Reprinted from <a href="https://www.ncbi.nlm.nih.gov/pubmed/?term=25446321">Whitmore, S.S., Wagner, A.H., DeLuca, A.P., Drack, A.V., Stone, E.M., Tucker, B.A., Zeng, S., Braun, T.A., Mullins, R.F., Scheetz, T.E., 2014. Transcriptomic analysis across nasal, temporal, and macular regions of human neural retina and RPE/choroid by RNA-Seq. Experimental Eye Research</a>. Used under <a href="http://creativecommons.org/licenses/by-nc-sa/3.0/">Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported </a>license.</p> <p>Additional RNA sequencing was performed on temporal, macular, nasal, inferior, and superior retina from a fifth subject and is included in this dataset. See original publication for details.</p>
| phs001151 | dbGaP
Project description:Age related macular degeneration (AMD) is the most prominent cause of blindness in the developed countries. Vision loss in the advanced stages of the disease is caused by atrophy of retinal photoreceptors, overlaying retinal pigment epithelium (RPE) and choroid endothelial cells. The molecular events that underline the development of these cell types from in utero to adult as well as the progression from the asymptomatic, to intermediate and advanced stages AMD are not yet fully understood. We performed single cell RNA-Sequencing (Seq) of human fetal and adult RPE and choroid, profiling in detail all the cell types and elucidating proliferation, differentiation, antigen pathway presentation and immunomodulation events that characterise the first half of human gestation. Our data demonstrate that progression from fetal to adult state is characterised by an increase in expression of genes involved in oxidative stress response and detoxification from heavy metals, suggesting a better defence against oxidative stress in the adult RPE and choroid tissues. Single cell comparative transcriptional analysis between an intermediate AMD patient and unaffected subject revealed specific loss of RPE and melanocytes in the macular region. While the CECs loss was not supported by our single cell RNA-Seq data, pathway enrichment analyses supported the onset of apoptosis in these cells, suggesting that during the course of AMD pathogenesis, endothelial cells are the most likely cell type to atrophy in the macula of AMD patients. Together these finds provide a rich resource for enhancing our understanding the development of RPE and choroid and the role they play in AMD progression and pathogenesis
2023-01-19 | GSE210543 | GEO
Project description:Purpose: Age-related degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE)/choroid from early AMD and control maculas using exon-based arrays. Methods: Gene expression levels in nine early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using DAVID, and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. CFH genotype was also assessed and differential expression was analyzed with respect to high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Results: Seventy-five genes were identified as differentially expressed (raw p-value < 0.01; >50% fold change, mean log2 expression level in AMD or control M-bM-^IM-% median of all average gene expression values); however, no genes were significant (adj. p-value < 0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change < 0.5; raw p-value < 0.01), 18 genes were identified by DAVID analysis as associated with vision or neurological processes. GSEA of RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis with respect to CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p-value = 0.0008). Conclusions: GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout occurs early in the pathogenesis of AMD. Using AltAnalyze (ver. 2.0.7 beta), we analyzed nine early AMD and nine control eyes using Affymetrix Human Exon ST 1.0 arrays. Following initial processing in AltAnalyze, two control arrays were identified as potential outliers by tests implement in arrayQualityMetrics, a package for R.
2013-12-23 | E-GEOD-50195 | biostudies-arrayexpress
Project description:Young mice were compared to old mice (2 month vs 24 month) to determine gene changes that occur with aging in the mouse retinal pigmented epithelium/choroid of the eye. Keywords = retinal pigmented epithelium Keywords = aging Keywords = choroid
2010-06-05 | E-GEOD-565 | biostudies-arrayexpress
Project description:Purpose: Age-related degeneration (AMD) is a major cause of blindness in developed countries. The molecular pathogenesis of early events in AMD is poorly understood. We investigated differential gene expression in samples of human retinal pigment epithelium (RPE)/choroid from early AMD and control maculas using exon-based arrays. Methods: Gene expression levels in nine early AMD and nine control human donor eyes were assessed using Affymetrix Human Exon ST 1.0 arrays. Two controls did not pass quality control and were removed. Differentially expressed genes were annotated using DAVID, and gene set enrichment analysis (GSEA) was performed on RPE-specific and endothelium-associated gene sets. CFH genotype was also assessed and differential expression was analyzed with respect to high AMD risk (YH/HH) and low AMD risk (YY) genotypes. Results: Seventy-five genes were identified as differentially expressed (raw p-value < 0.01; >50% fold change, mean log2 expression level in AMD or control ≥ median of all average gene expression values); however, no genes were significant (adj. p-value < 0.01) after correction for multiple hypothesis testing. Of 52 genes with decreased expression in AMD (fold change < 0.5; raw p-value < 0.01), 18 genes were identified by DAVID analysis as associated with vision or neurological processes. GSEA of RPE-associated and endothelium-associated genes revealed a significant decrease in genes typically expressed by endothelial cells in the early AMD group compared to controls, consistent with previous histologic and proteomic studies. Analysis with respect to CFH genotype indicated decreased expression of ADAMTS9 in eyes with high-risk genotypes (fold change = -2.61; raw p-value = 0.0008). Conclusions: GSEA results suggest that RPE transcripts are preserved or elevated in early AMD, concomitant with loss of endothelial cell marker expression. These results are consistent with the notion that choroidal endothelial cell dropout occurs early in the pathogenesis of AMD.
2013-12-23 | GSE50195 | GEO
Project description:Young mice were compared to old mice (2 month vs 24 month) to determine gene changes that occur with aging in the mouse retinal pigmented epithelium/choroid of the eye. Keywords = retinal pigmented epithelium Keywords = aging Keywords = choroid Keywords: other
2003-09-30 | GSE565 | GEO
Project description:Epigenomic Profiling and Single_Nucleus_RNA_Seq of Adult Human Retina, Macula, and RPE/Choroid
| PRJNA573850 | ENA
Project description:The retinas of simian primates include a specialized, cone-rich, macula which regards the central visual field and mediates high acuity and colour vision. A prominent feature of the macula is the fovea centralis - a 1 mm-wide, avascular depression in the inner retinal surface that corresponds with a local absence of rods and a peak spatial density of cones in the outer photoreceptor layer. The arrangement of macular photoreceptors, and their specialized ‘midget’ circuits, are the neural substrate for high resolution vision in primates. Macular-specific photoreceptor loss and abnormal blood vessel growth within the macula are the major causes of untreatable vision loss worldwide. However, the genes that regulate specialization of the macula, and the causes of its vulnerability to degeneration, remain obscure. Microarrays were used to compare gene expression between macula and non-macular regions during a critical phase of human retinal vascular development. Keywords: Comparison of developing anatomical regions
2008-12-30 | GSE12621 | GEO
Project description:Purpose To examine how circulating immune mediators in vivo may affect gene and protein expression at the retinal pigment epithelium (RPE)/choroid interface. Methods Young mice were systemically infected with lymphocytic choriomeningitis virus (LCMV) or continuously infused with interferon (IFN)γ. RPE/choroid was isolated and analyzed with whole-transcriptome gene expression microarrays. Selected gene expression findings were validated at the protein level. Results Both the systemic immune activation from virus infection and the sterile systemically increased level of IFNγ resulted in increased expression of chemokine ligands, chemokine receptors and early complement components in isolates of RPE/choroid. These findings were largely absent from LCMV-infected mice deficient in either the interferon α/β receptor or IFNγ. Conclusions Together, these findings demonstrate that acute systemic immune activation results in a local response at the RPE/choroid interface that may include chemokine-dependent recruitment of inflammatory cells and engagement of the complement system. This may represent a link between the systemic low-grade inflammation and the retinal pathology observed in several multifactorial entities such as aging, age-related macular degeneration (AMD) and diabetes.
2018-12-31 | GSE73519 | GEO