Transcriptomic analysis of human retinal detachment (RD) reveals both inflammation and photoreceptor death
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE28133 | GEO | 2012/03/06
SECONDARY ACCESSION(S): PRJNA139819
REPOSITORIES: GEO
Similar Datasets
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: Not available
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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: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:Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus. Here, we define the transcriptional changes during differentiation, especially those caused by detachment from the substratum. Using comprehensive transcriptional profiling, we revisited the effects of detachment as a differentiation signal to keratinocytes. We identified the genes regulated by detachment, the corresponding ontological categories and, using metaanalysis, compared the genes and categories to those regulated by other pro-differentiating stimuli. We identified 762 genes overexpressed in suspended keratinocyte, including known and novel differentiation markers, and 1427 in attached cells, including basal layer markers. Detachment induced epidermis development, cornification and desmosomal genes, but also innate immunity, proliferation inhibitors, transcription regulators and MAPKs; conversely the attached cells overexpressed cell cycle, anchoring, motility, splicing and mitochondrial genes, and both positive and negative regulators of apoptosis. Metaanalysis identified which detachment-regulated categories overlap with those induced by suprabasal location in vivo, by reaching confluency in vitro, and by inhibition of JUN kinases. Attached and in vivo basal cells shared overexpression of mitochondrial components. Interestingly, melanosome trafficking components were also overexpressed in the attached and in vivo basal keratinocytes. Reaching confluency did not affect adhesion and ECM proteins. Lipid metabolism and steroid metabolism were induced by confluency and by JNK inhibition, respectively. These results suggest that specific pro-differentiation signals induce specific features of the keratinization process, which are in vivo orchestrated into harmonious epidermal homeostasis. Human epidermal keratinocytes are grown in standard growth medium either attached in tissue culture plates, or suspended, in the same medium, in bacteriological plates. After 48 hrs, attached and suspended cultures were harvested and their transcriptomes compared.
2014-04-25 | E-GEOD-57045 | biostudies-arrayexpress
Project description:Epidermis, a continuously self-renewing and differentiating organ, produces a protective stratum corneum that shields us from external chemical, physical and microbial threats. Epidermal differentiation is a multi-step process regulated by influences, some unknown, others insufficiently explored. Detachment of keratinocytes from the basement membrane is one such pro-differentiation stimulus. Here, we define the transcriptional changes during differentiation, especially those caused by detachment from the substratum. Using comprehensive transcriptional profiling, we revisited the effects of detachment as a differentiation signal to keratinocytes. We identified the genes regulated by detachment, the corresponding ontological categories and, using metaanalysis, compared the genes and categories to those regulated by other pro-differentiating stimuli. We identified 762 genes overexpressed in suspended keratinocyte, including known and novel differentiation markers, and 1427 in attached cells, including basal layer markers. Detachment induced epidermis development, cornification and desmosomal genes, but also innate immunity, proliferation inhibitors, transcription regulators and MAPKs; conversely the attached cells overexpressed cell cycle, anchoring, motility, splicing and mitochondrial genes, and both positive and negative regulators of apoptosis. Metaanalysis identified which detachment-regulated categories overlap with those induced by suprabasal location in vivo, by reaching confluency in vitro, and by inhibition of JUN kinases. Attached and in vivo basal cells shared overexpression of mitochondrial components. Interestingly, melanosome trafficking components were also overexpressed in the attached and in vivo basal keratinocytes. Reaching confluency did not affect adhesion and ECM proteins. Lipid metabolism and steroid metabolism were induced by confluency and by JNK inhibition, respectively. These results suggest that specific pro-differentiation signals induce specific features of the keratinization process, which are in vivo orchestrated into harmonious epidermal homeostasis.
2014-04-25 | GSE57045 | GEO
Project description:Dry age-related macular degeneration (AMD) is characterized by the progressive loss of retinal pigment epithelium cells in the macula, leading to photoreceptor degeneration and loss of central vision. Current treatments can only slow disease progression in some cases, but once photoreceptors are damaged, vision loss becomes irreversible. Therefore, there is an urgent need to develop therapies that prevent photoreceptor cell death. A critical step toward this goal is establishing pathophysiologically relevant human disease models for therapeutic testing. In this study, we developed a human- induced pluripotent stem cell-derived retinal organoid (RO) model that recapitulates key aspects of AMD-associated photoreceptor degeneration. Since cigarette smoking is a major environmental risk factor for AMD, we exposed ROs to cigarette smoke extract (CSE) to induce cellular stress. CSE treatment resulted in increased reactive oxygen species, mitochondrial membrane depolarization, and cell death primarily in the outer nuclear layer. Photoreceptor degeneration in this model involves the activation of the intrinsic apoptotic pathway and ferroptosis, which is accompanied by lipid peroxidation and dysregulation of the glutathione system. Comprehensive proteomic analysis confirmed the dysregulation of metabolic and stress response pathways. The integration of this model with robust, quantitative outcome measures in live ROs offers a powerful platform for preclinical drug screening and therapeutic evaluation.
2026-04-14 | PXD063075 | Pride
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