Metabolomics Workbench ST000699 - GNPS - Human vitreous amino acid & lipid analysis
Ontology highlight
ABSTRACT:
INSTRUMENT(S): QTOF - NEGATIVE, Q - POSITIVE, QTOF - POSITIVE
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Maureen Kachman
PROVIDER: MSV000082720 | GNPS | Thu Aug 02 17:19:00 BST 2018
REPOSITORIES: GNPS
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Project description:Human vitreous was collected in the OR at time of indicated surgery. No treatments were involved. Diagnoses are: epiretinal membranes (ERM); proliferative diabetic retinopathy (PDR); retinal detachment (RD)
2017-06-19 | ST000699 | MetabolomicsWorkbench
Project description:Background: Proliferative diabetic retinopathy (PDR) is hallmarked by the formation of retinal neovascularization (RNV) membranes, which can lead to a tractional retinal detachment, the primary reason for severe vision loss in end-stage disease. The aim of this study was to characterize the molecular and cellular features of RNV in order to unravel potential novel drug treatments for PDR. Methods: A total of 42 patients undergoing vitrectomy for PDR, macular pucker or macular hole (control patients) were included in this study. The surgically removed RNV and epiretinal membranes were analyzed by RNA sequencing, single-cell based Imaging Mass Cytometry and conventional immunohistochemistry. Since macrophages were found to be abundant in RNV tissue, vitreal macrophages, also known as hyalocytes, were isolated from the vitreous of patients with PDR by flow cytometry, cultivated and characterized by immunhistochemistry. A bioinformatical drug repurposing approach was applied, in order to identify novel drug options for end-stage diabetic retinopathy disease. Results: The in-depth transcriptional and single-cell protein analysis of diabetic RNV tissue samples revealed an accumulation of endothelial cells, macrophages and myofibroblasts as well as an abundance of secreted ECM proteins such as SPARC, FN1 and several types of collagen in RNV tissue. The immunohistochemical staining of cultivated vitreal hyalocytes from patients with PDR showed that hyalocytes express α-SMA (alpha-smooth muscle actin), a classic myofibroblast marker. According to our drug repurposing analysis, imatinib emerged as a potential drug option for future treatment of PDR. Conclusion: This study delivers the first in-depth transcriptional and single-cell proteomic characterization of RNV tissue samples. Our data suggest an important role of hyalocyte-to-myofibroblast transdifferentiation in the pathogenesis of diabetic vitreoretinal disease and suggests their modulation as a novel possible clinical approach.
2021-10-31 | GSE179568 | GEO
Project description:Proliferative diabetic retinopathy (PDR) is a vision-threatening disorder characterized by the formation of cicatricial fibrovascular membranes leading to traction retinal detachment. Despite the recent advance in the treatment of PDR such as vitreoretinal surgery with use of anti-vascular endothelial growth factor (VEGF) drug as an adjunct, it still remains vision-threatening disease. In order to identify genes associated with the pathogenesis of PDR, we performed gene expression analyses in fibrovascular membrane in patients with PDR using DNA microarray technology. This study was approved by the Ethics Committee of the Kyushu University Hospital and Fukuoka University Chikushi Hospital, and the surgical specimens were handled in accordance with the ethical standards of the 1989 Declaration of Helsinki. All patients gave informed consent before inclusion in the study. Fibrovascular membranes (FVMs) were surgically dissected from the retinal surface with horizontal scissors of patients with PDR undergoing pars plana vitrectomy. These specimens were classified into active and inactive according to the clinical findings of neovascularization (NV) in the FVMs.Total RNA were extracted from the FVMs. RNA from human retina was obtained from Clontech (Palo Alto, CA).
2014-08-16 | E-GEOD-60436 | biostudies-arrayexpress
Project description:Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective treatments for type 2 diabetes, effectively lowering glucose without weight gain and with low risk for hypoglycemia. However, their influence on the retinal neurovascular unit remains unclear. In this study we analyzed the effects of the GLP-1 RA lixisenatide in a rat model of type-1 like diabetic retinopathy. Vasculo- and neuroprotective effects were assessed in experimental diabetic retinopathy and high glucose-cultivated C. elegans, respectively. In STZ-diabetic Wistar rats acellular capillaries and pericytes (quantitative retinal morphometry), neuroretinal function (mfERG), macroglia (GFAP western blot) and microglia (immunohistochemistry) quantification, methylglyoxal (LC-MS/MS) and retinal gene expressions (RNA-sequencing) were determined. The antioxidant properties of lixisenatide were tested in C. elegans. Lixisenatide had no effect on glucose metabolism. Lixisenatide preserved the retinal vasculature and neuroretinal function. The macro- and microglial activation was mitigated. Lixisenatide normalized some gene expression changes in diabetic animals to control levels. Ets2 was identified as a regulator of inflammatory genes. In C. elegans lixisenatide showed the antioxidative property. In summary, these data suggest that lixisenatide has a protective effect on the diabetic retina, most likely due to a combination of neuroprotective, anti-inflammatory and antioxidative effects of lixisenatide on the neurovascular unit.
2023-07-05 | GSE236333 | GEO
Project description:Retinal neovascularization is a severe complication of proliferative diabetic retinopathy. We have previously identified that miRNAs is directly involved in the development of retinal neovascularization. Here, we explored the role of miRNAs and its underlying mechanism in modulating angiogenesis.
2021-10-01 | GSE139947 | GEO
Project description:Proliferative diabetic retinopathy (PDR) is a vision-threatening disorder characterized by the formation of cicatricial fibrovascular membranes leading to traction retinal detachment. Despite the recent advance in the treatment of PDR such as vitreoretinal surgery with use of anti-vascular endothelial growth factor (VEGF) drug as an adjunct, it still remains vision-threatening disease. In order to identify genes associated with the pathogenesis of PDR, we performed gene expression analyses in fibrovascular membrane in patients with PDR using DNA microarray technology.
2014-08-16 | GSE60436 | GEO
Project description:Diabetic retinopathy (DR), a leading cause of irreversible vision loss in the working-age population, is an inflammatory, neuro-vascular complication of diabetes with poorly understood mechanism. N6-methyladenosine (m6A) modification plays crucial roles in biological and pathological events, while its role in DR remain elusive. Herein, we identified the pathological involvement of m6A demethylase FTO in DR. FTO expression was elevated in proliferative membranes of DR patients, endothelial cells (EC) under diabetic stress, and retinal vessels of diabetic murine models. FTO overexpression in EC promoted EC cycle progression and tip cell formation to facilitate angiogenesis in vitro, in mice and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetes-induced microvascular leakage, and mediated EC-microglia crosstalk to induce retinal inflammation and subsequent neurodegeneration in vivo and in vitro. Mechanistically, FTO regulated EC features depending on its demethylation activity via modulating CDK2 mRNA stability with YTHDF2 as the reader. Moreover, FTO up-regulation in EC under diabetic conditions was driven by lactic acid mediated histone lactylation. FB23-2, which inhibits FTO’s m6A demethylase activity, suppressed diabetes associated endothelial phenotypes in vitro and in vivo. Noteworthy, we developed a novel macrophage membrane coated and PLGA-Dil based nanoplatform encapsulating FB23-2 for systemic administration, and confirmed its targeting and therapeutic efficacy in mice. Collectively, our study demonstrated an FTO-mediated regulatory network that coordinates EC biology and retinal homeostasis in DR, providing a promising nanotherapeutic approach for DR treatment. Diabetic retinopathy (DR), a leading cause of irreversible vision loss in the working-age population, is an inflammatory, neuro-vascular complication of diabetes with poorly understood mechanism. N6-methyladenosine (m6A) modification plays crucial roles in biological and pathological events, while its role in DR remain elusive. Herein, we identified the pathological involvement of m6A demethylase FTO in DR. FTO expression was elevated in proliferative membranes of DR patients, endothelial cells (EC) under diabetic stress, and retinal vessels of diabetic murine models. FTO overexpression in EC promoted EC cycle progression and tip cell formation to facilitate angiogenesis in vitro, in mice and in zebrafish. FTO also regulated EC-pericyte crosstalk to trigger diabetes-induced microvascular leakage, and mediated EC-microglia crosstalk to induce retinal inflammation and subsequent neurodegeneration in vivo and in vitro. Mechanistically, FTO regulated EC features depending on its demethylation activity via modulating CDK2 mRNA stability with YTHDF2 as the reader. Moreover, FTO up-regulation in EC under diabetic conditions was driven by lactic acid mediated histone lactylation. FB23-2, which inhibits FTO’s m6A demethylase activity, suppressed diabetes associated endothelial phenotypes in vitro and in vivo. Noteworthy, we developed a novel macrophage membrane coated and PLGA-Dil based nanoplatform encapsulating FB23-2 for systemic administration, and confirmed its targeting and therapeutic efficacy in mice. Collectively, our study demonstrated an FTO-mediated regulatory network that coordinates EC biology and retinal homeostasis in DR, providing a promising nanotherapeutic approach for DR treatment.
2023-05-15 | GSE232135 | GEO
Project description:The underlying pathomechanisms in diabetic retinopathy (DR) remains incompletely understood. The aim of this study was to add to the current knowledge about the particular role of retina Müller glial cells (RMG) in the initial processes of DR. Applying a mass spectrometric workflow, we investigated proteome changes of primary porcine RMG under short term diabetic cell culture treatment. We revealed global changes in RMG proteome indicated by a fundamental remodeling of ECM and focal adhesion processes which potentially leads to destabilization of the retinal inner limiting membrane. This is in line with our previous findings of a disrupted ILM in the retinae of a diabetic pig model and suggests an involvement of RMG in this process. Additionally, employing porcine organotypic retinal explant cultures, we demonstrate a specific decrease of RMG-associated SPP1 expression as a result of osmotic challenge induced by high glucose levels. We assume a loss of neuroprotective potential administrated by RMG and subsequent acceleration of neurodegenerative processes in DR.
2021-04-06 | PXD015879 | Pride
Project description:Diabetic retinopathy is one of the leading causes of blindness in diabetic patients. Emerging evidence suggests that retinal neurodegeneration is an early event in the pathogenesis of diabetic retinopathy, but the underlying causes of neuronal loss are unknown. To unravel potential mechanisms underlying early retinal neurodegeneration in diabetic retinopathy, a gene expression profiling study was undertaken to compare the gene expression in retinas of 8-week db/db diabetic mice with that of lean non-diabetic littermates. Retinas were obtained from 8-week db/db diabetic mice and age-matched lean non-diabetic controls. Total RNA was extracted and processed for being hybridized onto affymetrix DNA microarrays.
2014-02-27 | E-GEOD-55389 | biostudies-arrayexpress
Project description:Rat Retinal Müller cells from diabetic rats (diabetes duration 6 months) compared to Rat Retinal Müller cells from healthy rats. Diabetes was induced by streptozotozine. Diabetic rats were treated with small doses of insulin to prevent catabolism. Keywords: ordered
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