The mouse retinal pigment epithelium mounts an innate immune defense response following retinal detachment
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ABSTRACT:
PROVIDER: PRJNA1084835 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28245905_1.fastq.gz | Fastqsanger.gz | |||
| SRR28245905_2.fastq.gz | Fastqsanger.gz | |||
| SRR28245906_1.fastq.gz | Fastqsanger.gz | |||
| SRR28245906_2.fastq.gz | Fastqsanger.gz | |||
| SRR28245907_1.fastq.gz | Fastqsanger.gz |
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Project description:The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNAseq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd). were defined as mRNA with a significant (padj≤0.05) fold change (FC) of 0.67≥FC≥1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, andtight junctions were down regulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNAseq results. Thus, the RPE quickly down-regulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space and the opsonization of orphaned outer segments following RD.
2024-04-03 | GSE261021 | GEO
Project description:The retinal pigment epithelium (RPE) maintains photoreceptor viability and function, completes the visual cycle, and forms the outer blood-retinal barrier (oBRB). Loss of RPE function gives rise to several monogenic retinal dystrophies and contributes to age-related macular degeneration. Retinal detachment (RD) causes separation of the neurosensory retina from the underlying RPE, disrupting the functional and metabolic relationships between these layers. Although the retinal response to RD is highly studied, little is known about how the RPE responds to loss of this interaction. RNA sequencing (RNA-Seq) was used to compare normal and detached RPE in the C57BL6/J mouse. The naïve mouse RPE transcriptome was compared to previously published RPE signature gene lists and from the union of these 14 genes (Bmp4, Crim1, Degs1, Gja1, Itgav, Mfap3l, Pdpn, Ptgds, Rbp1, Rnf13, Rpe65, Slc4a2, Sulf1 and Ttr) representing a core signature gene set applicable across rodent and human RPE was derived. Gene ontology enrichment analysis (GOEA) of the mouse RPE transcriptome identified expected RPE features and functions, such as pigmentation, phagocytosis, lysosomal and proteasomal degradation of proteins, and barrier function. Differentially expressed genes (DEG) at 1 and 7 days post retinal detachment (dprd) were defined as mRNA with a significant (padj≤0.05) fold change (FC) of 0.67 ≥ FC ≥ 1.5 in detached versus naïve RPE. The RPE transcriptome exhibited dramatic changes at 1 dprd, with 2297 DEG identified. The KEGG pathways and biological process GO groups related to innate immune responses were significantly enriched. Lipocalin 2 (Lcn2) and several chemokines were upregulated, while numerous genes related to RPE functions, such as pigment synthesis, visual cycle, phagocytosis, and tight junctions were downregulated at 1 dprd. The response was largely transient, with only 18 significant DEG identified at 7 dprd, including upregulation of complement gene C4b. Validation studies confirmed RNA-Seq results. Thus, the RPE quickly downregulates cell-specific functions and mounts an innate immune defense response following RD. Our data demonstrate that the RPE contributes to the inflammatory response to RD and may play a role in attraction of immune cells to the subretinal space.
| S-EPMC10964713 | biostudies-literature
Project description:Retinal detachment is a major cause of blindness due to penetrating trauma and ocular inflammation, and is often observed in many patients following cataract extraction surgery. When the retinal photoreceptors detach from their epithelium, stress signals and apoptotic pathways are initiated that will lead to loss of vision, however accelerating the reattachment of these cells can prevent photoreceptor death and subsequent vision loss. To determine the genes involved in this process, we performed a microarray screen using a mouse model or retinal detachment in conjunction with a P2Y2 agonist previously demonstrated to hasten retinal reattachment. Experiment Overall Design: We conducted a microarray screen to identify genes involved in promoting faster resolution of retinal detachment. Subretinal detachment was induced in Balb/cJ mice by subretinal injection of 1 uL saline or delivery of 1 uL of 10uM INS37217/Saline to cause detachment and expedite the rate of recovery. We performed this study at three timepoints: 2 hrs post-injection to identify early response genes; 24 hrs post-detachment when the retina has reattached, but still grossly misfolded; and 7 days post-detachment when the misfolding has been resolved, but retinal function is merely 50% of wild-type function. We used each RNA pool (each containing >5 retinas) for GeneChip hybridization giving a total of 3 biological replicates for each treatment at each timepoint. For each GeneChip, we labeled 7 ug of total RNA according to the manufacturerâs specifications (Affymetrix Inc.).
2008-06-14 | E-GEOD-5766 | biostudies-arrayexpress
Project description:We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment. Data analysis reveals major involvement of the immune response in the disease and interindividual variation was monitored to unravel a second crucial aspect of the pathological process, the death of photoreceptor cells. In total 38 surgical specimens (samples) were analyzed, 19 represent biopsies from patients with retinal detachment (RD) and 19 represent contral samples without retinal detachment.
2012-03-06 | E-GEOD-28133 | biostudies-arrayexpress
Project description:Retinal detachment is a major cause of blindness due to penetrating trauma and ocular inflammation, and is often observed in many patients following cataract extraction surgery. When the retinal photoreceptors detach from their epithelium, stress signals and apoptotic pathways are initiated that will lead to loss of vision, however accelerating the reattachment of these cells can prevent photoreceptor death and subsequent vision loss. To determine the genes involved in this process, we performed a microarray screen using a mouse model or retinal detachment in conjunction with a P2Y2 agonist previously demonstrated to hasten retinal reattachment. Keywords: disease state analysis and therapeutic analysis
2007-11-10 | GSE5766 | GEO
Project description:The vitreous humor can provide important information about physiological and pathophysiological processes within the eye, particularly concerning the retina. Despite the widespread prevalence of various vitreoretinal diseases, that can ultimately lead to blindness, there is not a clear understanding of many molecular processes underlying these conditions. Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults in U.S. and developed world. It can result in macular edema and tractional retinal detachment (TRD). Hyperglycemia can induce damage to retinal cells and capillary closure, leading to retinal ischemia and elevated levels of nitric oxide (NO). This, in turn, increases the activity of protein kinase C and the levels of different growth factors, including vascular endothelial growth factor (VEGF). These events can stimulate the development of new blood vessels from existing matured vessels, which are subsequently encompassed by glial cells and fibrous proliferation, potentially leading to TRD. Rhegmatogenous retinal detachment (RD) is the separation of neuroretinal layers from the retinal pigment epithelium (RPE), induced by a break in the neuroretina that allows the influx of liquefied vitreous. In the detached retina outer layers become ischemic and photoreceptors undergo cell death mainly by apoptosis. Moreover, 3–4 days after retinal detachment, a peak of proliferation of non-neuronal cells, such as astrocytes, endothelial cells, pericytes, and microglia, can be observed. A possible complication of rhegmatogenous retinal detachment is proliferative vitreoretinopathy (PVR), a condition defined by the growth and contraction of cellular membranes within the vitreous cavity. Fibroblast or fibrocyte cells have been detected in epiretinal membranes in PVR, and the origin of these cells is debated. Different authors have suggested that they could be transformed RPE cells or metaplastic vascular endothelial cells, glial cells, macrophages, or hyalocytes. Macular pucker is a condition defined by an epiretinal membrane described as a semi-translucent avascular membrane over the internal limiting membrane (ILM) on the surface of the retina. It can be idiopathic or secondary to various conditions, such as trauma, intraocular inflammation, etc. The initial event that can induce an idiopathic pucker is posterior vitreous detachment (PVD), which can cause dehiscence in the internal limiting membrane. Through this opening, microglial cells move to the preretinal surface, where they can interact with hyalocytes and laminocytes. Subsequent transdifferentiation to fibroblast-like cells leads to the development of an epiretinal membrane.
2025-02-24 | PXD050611 | Pride
Project description:Transcriptomic analysis of transferrin protective effect during retinal detachment in mice.
2019-08-31 | GSE102824 | GEO
Project description:Here, we performed molecular pathology analysis of the vitreous proteomes collected from 127 patients with RRD using SWATH-mass spectrometry. For comparison, samples of neurodegenerative vitreoretinal interface eyes (MH, Pucker) and proliferative diabetic retinopathy eyes with tractional-retinal detachment (PDR-TRD) were used as a control.
2020-11-05 | MSV000086412 | MassIVE
Project description:Retinal detachment is a severe eye condition characterized by the detachment of the neurosensory retina from the retinal pigment epithelium and caused by retinal tears. Pars plana vitrectomy is the elective surgical procedure during which vitreous humor, a fluid which shapes the eye globe and supports mechanically the adherence of the retina to the posterior chamber of the eye, is collected. Therefore, profiling of the vitreous humor proteome of subjects diagnosed with retinal detachment is supposed to provide molecular evidence on the pathobiology of the disease and on its secondary complications, such as proliferative vitreo-retinopathy, which predispose to recurrent RD (observed in 20% of cases), a sight threatening condition. Herein, we investigated the perturbations of vitreous proteome between subjects affected by primary retinal detachment and controls by shot-gun proteomics approaches. Proteomic datasets were first analyzed and searched for global proteome changes. Thereafter, starting from the assumption that the disease could be sustained by altered proteolytic processing of structural and non-structural elements of the VH, mining of N- and C-termini was performed to uncover endogenous proteolytic events underscoring the disease condition. The search retrieved evidence of a wide repertoire of either previously characterized or uncharacterized proteolytic events. Most notably, comparison of the N- and C-termini landscape between experimental groups highlighted robust alterations in the repertoire of cleaved proteins. Further strengthened by immunoblotting studies on a select panel of proteins, the data envisage that retinal detachment is promoted or characterized, as a secondary process, by proteolytic-based alterations of structural and non-structural components involved in the regulation of immune process, proteases inhibition and most notably, angiogenesis.
2025-10-20 | PXD057155 | Pride
Project description:Retinal pigment epithelial cells are critical for eye function and loss of cell function is linked to age-related blindness. Relatively little is known about the transcriptional regulatory networks in these cells. The datasets presented here are ChIP-seq experiments for RNA polymerase II , transcription factors and histone modifications in human retinal pigment epithelial cells. ChIP-Seq for transcription factors, RNA polymerase, histone modifications and CTCF in retinal pigment epithelial cells
2014-08-03 | E-GEOD-60024 | biostudies-arrayexpress