Deciphering Primate Retinal Aging at Single-Cell Resolution
Ontology highlight
ABSTRACT:
ORGANISM(S): Macaca fascicularis
PROVIDER: GSE113917 | GEO | 2020/10/20
REPOSITORIES: GEO
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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:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.
2023-07-15 | GSE236220 | GEO
Project description:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.
2023-07-15 | GSE236219 | GEO
Project description:The activity and survival of retinal photoreceptors depend on support functions performed by the retinal pigment epithelium (RPE) and on oxygen and nutrients delivered by blood vessels in the underlying choroid. By combining single cell and bulk RNA sequencing, we categorized mouse RPE/choroid cell types and characterized the tissue-specific transcriptomic features of choroidal endothelial cells. We found that choroidal endothelium adjacent to the RPE expresses high levels of Indian Hedgehog, and identified its downstream target as stromal GLI1+ mesenchymal stem cell-like cells. Genetic impairment of Hedgehog signaling in vivo induced significant loss of choroidal mast cells, as well as an altered inflammatory response and exacerbated visual function defects after retinal damage. Our studies reveal the cellular and molecular landscape of adult RPE/choroid and uncover a Hedgehog-regulated choroidal immunomodulatory signaling circuit. These results open new avenues for the study and treatment of retinal vascular diseases and choroid-related inflammatory blinding disorders.
2020-02-28 | GSE135167 | GEO
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Experiment Overall Design: We compared the gene expression of retinal pigmental epithelium/choroid from young and old animals. There were 4 samples from young mice and 4 samples from old mice. Each sample contained 4 retinal pigmental epithelium/choroid from 2 animals
2008-06-11 | E-GEOD-10965 | biostudies-arrayexpress
Project description:This experiment analyzes the mirnome of 16 retina samples and 2 Retinal Pigment Epithelium (RPE)/choroid from non-visually impaired post-mortem donors, by using smallRNAseq on a Illumina platform. The aim was to establish the catalogue of normal retina-expressed miRNAs, determine their relative abundance, and identify miRNA variants (isomiRs).
2016-01-27 | E-MTAB-3792 | biostudies-arrayexpress
Project description:Purpose: The aim of this study was to give a comprehensive overview on spatial distribution of gene expression in the adult mouse retina and integrate this information into existing retinal gene expression databases. Methods: Total RNA was collected by laser capture microdissection from the ganglion cell layer, inner nuclear layer, photoreceptors and the retinal pigmented epithelium of adult mice and was analyzed by oligonucleotide microarrays. The results were validated by quantitative real time PCR and in situ hybridization. Results: The applied method resulted in good separation of cells of different retinal layers. The spatial distribution of gene expression was determined on a global scale in the retina and the RPE. Our results show good correlation with previously reported retinal gene expression and describe genes not yet characterized in the context of the retina. Conclusions: The complexity of the vertebrate retina makes it necessary to determine not only temporal but spatial distributions of gene expression .Our work expands the already significant but still incomplete knowledge of retinal gene expression and hopefully facilitates functional characterization of key factors of retinal development and maintenance. Laser capture microdissected regions of the adult mouse neuronal retina and retinal pigmented epithelium were subjected to microarray analysis. 5 conditions were investigated: ganglion cell layer (GCL, 3 biological replicates), innner nuclear layer (INL, 3 biological replicates), photoreceptor layer from Blk6 (PR-WT, 3 biological replicates) and NrlKO animals (PR-Nrl, 2 biological replicates) and retinal pigmented epithelium (RPE, 1 biological replicate). All samples are co-hybridized with a reference sample (retina). 2 or 3 technical replicates were used for each biological sample. technical replicate - labeled-extract: GC1-1, GC1-2, GC1-3 technical replicate - labeled-extract: GC2-1, GC2-2, GC2-3 technical replicate - labeled-extract: GCpool-1, GCpool-2, GCpool-3 technical replicate - labeled-extract: INL1-1, INL1-2, INL1-3 technical replicate - labeled-extract: INL2-1, INL2-2, INL2-3 technical replicate - labeled-extract: INLpool-1, INLpool-2, INLpool-3 technical replicate - labeled-extract: PR-Nrl1-1, PR-Nrl1-2 technical replicate - labeled-extract: PR-Nrl2-1, PR-Nrl2-2, PR-Nrl2-3 technical replicate - labeled-extract: PR-WT1-1, PR-WT1-2, PR-WT1-3 technical replicate - labeled-extract: PR-WT2-1, PR-WT2-2, PR-WT2-3 technical replicate - labeled-extract: PR-WTpool-1, PR-WTpool-2, PR-WTpool-3 technical replicate - labeled-extract: RPE-1, RPE-2, RPE-3
2009-12-31 | E-GEOD-19304 | biostudies-arrayexpress
Project description:Eye development and photoreceptor maintenance requires the retinal pigment epithelium (RPE), a thin layer of cells that underlies the neural retina. Despite its importance, RPE development has not been studied by a genomic approach. A microarray expression profiling methodology was established in this study for studying RPE development. The intact retina with RPE attached was dissected from developing embryos, and differentially expressed genes in RPE were inferred by comparing the dissected tissues with retinas without RPE using microarray and statistical analyses. We found 8810 probesets to be significantly expressed in RPE at 52 hours post-fertilization (hpf), of which 1443 might have biologically meaningful expression levels. Further, 78 and 988 probesets were found to be significantly over- or under-expressed in RPE respectively compared to retina. Also, 79.2% (38/48) of the known over-expressed probesets have been independently validated as RPE-related transcripts. The results strongly suggest that this methodology can obtain in vivo RPE specific gene expression from the zebrafish embryos and identify novel RPE markers. Experiment Overall Design: The gene expression levels of three independent replicates of retina with RPE attached consisting of ten samples each at 52hpf (WRR52) were compared with three independent pure retinal samples consisting of ten retinas each at 52hpf (WR52). The yield-adjusted WR52 expression values were assumed to be equivalent to the retinal contribution in WRR52 samples and deducted from WRR52 expression values to obtain estimations of RPE gene expression at 52hpf (RPE52). Differential gene expressions between RPE and retina were inferred by comparing the RPE52 estimates and WR52 expression values.
2008-06-13 | E-GEOD-5048 | biostudies-arrayexpress
Project description:Purpose: The outer blood-retina barrier is established through the coordinated terminal maturation of the retinal pigment epithelium (RPE), fenestrated choroid endothelial cells (ECs) and Bruch’s membrane, a highly organized basement membrane that lies between both cell types. Here we study the contribution of choroid ECs to this process by comparing their gene expression profile before (P5) and after (P30) the critical postnatal period when mice acquire mature visual function. Methods: ECs from P5 and P30 mice were labeled in vivo by retro-orbital injection of fluorescently-labeled anti-VE-Cadherin. After 10 minutes, mice were euthanized, eyeballs were enucleated and the anterior segment was discarded. After removal of the neural retina, RPE/choroid was mechanically dissected from the sclera and digested. ECs were isolated by flow cytometry and processed immediately for RNA extraction. Results: Transcriptome analyses show that whereas P5 choroid EC transcriptome is preferentially enriched in cell cycle- and chromosome-related transcripts, reflecting an immature phenotype, the transcriptome of adult (P30) choroid ECs is enriched in genes encoding proteins involved in ‘biological adhesion’, including a variety of extracellular matrix (ECM)-related genes. Conclusion: these results strongly suggest that mature choroid ECs actively participate in extracellular matrix assembly and regulation.
2017-05-01 | GSE95835 | GEO
Project description:To characterize underlying changes in the retinal pigment epithelium (RPE)/choroid with age, we produced gene expression profiles for the RPE/choroid and compared the transcriptional profiles of the RPE/choroid from young and old mice. The changes in the aged RPE/choroid suggest that the tissue has become immunologically active. Such phenotypic changes in the normal aged RPE/choroid may provide a background for the development of age-related macular degeneration. Keywords: age-related change
2008-03-29 | GSE10965 | GEO