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:BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.
| S-EPMC3235162 | 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: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:Detachment of photoreceptors from the retinal pigment epithelium is seen in various retinal disorders, resulting in photoreceptor death and subsequent vision loss. Cell death results in the release of endogenous molecules that activate molecular platforms containing caspase-1, termed inflammasomes. Inflammasome activation in retinal diseases has been reported in some cases to be protective and in others to be detrimental, causing neuronal cell death. Moreover, the cellular source of inflammasomes in retinal disorders is not clear. Here, we demonstrate that patients with photoreceptor injury by retinal detachment (RD) have increased levels of cleaved IL-1?, an end product of inflammasome activation. In an animal model of RD, photoreceptor cell death led to activation of endogenous inflammasomes, and this activation was diminished by Rip3 deletion. The major source of Il1b expression was found to be infiltrating macrophages in the subretinal space, rather than dying photoreceptors. Inflammasome inhibition attenuated photoreceptor death after RD. Our data implicate the infiltrating macrophages as a source of damaging inflammasomes after photoreceptor detachment in a RIP3-dependent manner and suggest a novel therapeutic target for treatment of retinal diseases.
| S-EPMC4650542 | biostudies-literature
Project description:Photoreceptor cell death and immune cell infiltration are two major events that contribute to retinal degeneration. However, the relationship between these two events has not been well delineated, primarily because of an inadequate understanding of the immunological processes involved in photoreceptor degeneration, especially that of peripheral leukocytes that infiltrate the subretinal space and retinal tissues. In this work, we characterized the role of leukocyte infiltration within the detached retina. We observed that CD45+ CD11b+ Ly6G+ neutrophils and CD45+ CD11b+ Ly6G- Ly6C+ monocytes are the predominant peripheral immune cell populations that infiltrate the retinal and subretinal space after detachment. Selective depletion of monocytes or neutrophils using cell-specific targeting is neuroprotective for photoreceptors. These results indicate that peripheral innate immune cells contribute to photoreceptor degeneration, and targeting these immune cell populations could be therapeutic during retinal detachment.
| S-EPMC10724298 | biostudies-literature
Project description:Transcriptomic analysis of transferrin protective effect during retinal detachment in mice.
2019-08-31 | GSE102824 | GEO