Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA309455 | ENA |
REPOSITORIES: ENA
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Project description:Diabetic retinopathy (DR) is the leading cause of blindness in working-age people. Pericyte loss is one of the pathologic cellular events in DR, which weakens the retinal microvessels. Damages to the microvascular networks are irreversible and permanent, thus further progression of DR is inevitable. In this study, we hypothesize that multipotent perivascular progenitor cells derived from human ESCs (hESC-PVPCs) improve the damaged retinal vasculature in the streptozotocin (STZ)-induced diabetic rodent models. We describe a highly efficient and feasible protocol to derive such cells using a natural selection method without cell sorting processes. As a cellular model of pericytes, hESC-PVPCs exhibited marker expressions such as CD140B, CD146, NG2, and functional characteristics of pericytes. Following a single intravitreal injection into diabetic Brown Norway (BN) rats, we demonstrate that the cells localized alongside typical perivascular regions of the retinal vasculature, and stabilized blood-retinal barrier (BRB) breakdown. Findings in this study highlight a therapeutic potential of hESC-PVPCs in DR by mimicking the role of pericytes in vascular stabilization.
2016-01-22 | GSE77114 | GEO
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:Human CD34+ stem cells are mobilized from bone marrow to sites of tissue ischemia and play an important role in tissue revascularization. This study used a murine model to test the hypothesis that intravitreal injection of human CD34+ stem cells harvested from bone marrow (BMSCs) can have protective effects in eyes with diabetic retinopathy. Streptozotocin-induced diabetic mice (C57BL/6J) were used as a model for diabetic retinopathy. Subcutaneous implantation of Alzet pump, loaded with Tacrolimus and Rapamycin, 5 days prior to intravitreal injection provided continuous systemic immunosuppression for the study duration to avoid rejection of human cells. Human CD34+ BMSCs were harvested from the mononuclear cell fraction of bone marrow from a healthy donor using magnetic beads. The CD34+ cells were labeled with enhanced green fluorescent protein (EGFP) using a lentiviral vector. The right eye of each mouse received an intravitreal injection of 50,000 EGFP-labeled CD34+ BMSCs or phosphate buffered saline (PBS). Simultaneous multimodal in vivo retinal imaging system consisting of fluorescent scanning laser ophthalmoscopy (enabling fluorescein angiography), optical coherence tomography (OCT) and OCT angiography was used to confirm the development of diabetic retinopathy and study the in vivo migration of the EGFP-labeled CD34+ BMSCs in the vitreous and retina following intravitreal injection. After imaging, the mice were euthanized, and the eyes were removed for immunohistochemistry. In addition, microarray analysis of the retina and retinal flat mount analysis of retinal vasculature were performed. The development of retinal microvascular changes consistent with diabetic retinopathy was visualized using fluorescein angiography and OCT angiography between 5 and 6 months after induction of diabetes in all diabetic mice. These retinal microvascular changes include areas of capillary nonperfusion and late leakage of fluorescein dye. Multimodal in vivo imaging and immunohistochemistry identified EGFP-labeled cells in the superficial retina and along retinal vasculature at 1 and 4 weeks following intravitreal cell injection. Microarray analysis showed changes in expression of 162 murine retinal genes following intravitreal CD34+ BMSC injection when compared to PBS-injected control. The major molecular pathways affected by intravitreal CD34+ BMSC injection in the murine retina included pathways implicated in the pathogenesis of diabetic retinopathy including Toll-like receptor, MAP kinase, oxidative stress, cellular development, assembly and organization pathways. At 4 weeks following intravitreal injection, retinal flat mount analysis showed preservation of the retinal vasculature in eyes injected with CD34+ BMSCs when compared to PBS-injected control. The study findings support the hypothesis that intravitreal injection of human CD34+ BMSCs results in retinal homing and integration of these human cells with preservation of the retinal vasculature in murine eyes with diabetic retinopathy.
2022-10-09 | GSE138719 | GEO
Project description:Pericytes confer vascular stability in the retina, and the loss of pericytes can cause the blood-retina barrier breakdown seen in diabetic retinopathy. To identify endothelial-specific genes expressed in pericyte-deprived retinal vessels, we purified genetically labeled endothelial cells from Tie2-GFP transgenic mice treated with neutralizing antibody against PDGFRb (APB5) and performed gene expression profiling using DNA microarray. To find out endothelial-specific genes associated with the loss of pericyte coverage, the comparison of microarray data was carried out between retinal endothelial cells (data from GSE27238) and APB5-treated retinal endothelial cells.
2017-01-01 | GSE86819 | GEO
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:The development of diabetic retinopathy is well characterized on a histological level. Early vascular alterations involve the loss of pericytes. Earlier mechanisms leading to the phenotype of diabetic retinopathy, which involves the complete neurovascular unit, are not yet fully understood. The gene expression data presented here is derived from microarrays and gives further insights into early genetic regulation in incipient diabetic retinopathy.
2019-01-17 | GSE111465 | GEO
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.
2014-02-27 | GSE55389 | GEO
Project description:We observe morphological changes of retinal microglia during early stages of diabetic retinopathy in STZ-treated mice. Therefore, in this experiment we assess the impact of STZ-induced diabetic retinopathy on retinal microglia transcriptome during early stages of disease.
2023-10-30 | GSE222005 | GEO
Project description:The mammalian retina contains an endogenous circadian clock system, located in various cell types. This system enables timing of a broad range of essential retinal functions to anticipate daily changes in environmental lighting conditions. Furthermore, the circadian clocks appear to promote retinal health. A leading cause of blindness in developed countries is diabetic retinopathy. While it is clear that diabetes affects the master clock and its circadian output in the SCN, the effect of diabetic retinopathy on the retinal clock system is unknown. To investigate the influence of diabetic retinopathy on circadian regulation of the retina at a genome-wide level, microarray analysis was used to compare retinal transcriptomes between light- and dark-adapted non-diabetic and diabetic mice.
2021-09-05 | GSE151350 | GEO
Project description:Comparative gene expression profiles of human retinal pericytes (HRMPC) and lipoaspirate derived mesenchymal stromal cells (adipose stromal cells, ASC) cultivated either in normal (1g/l) or high (4.5g/l) glucose medium to identify similarities and discrepancies and elucidate high glucose effects considering cell-based therapies in diabetic retinopathy. A hallmark of diabetic retinopathy is pericyte- dropout increased vascular permeability and progressive vascular occlusion. ASC and HRMVPC were cultured in NG or HG for 7 days. Then cells were trypsinized, washed and RNA isolated using Qiagen RNeasy mini Kit (Qiagen, Hilden, Germany). RNA quality was tested by capillary electrophoresis on an Agilent 2100 Bioanalyzer (Agilent) and high quality (RNA integrity values ≥ 9) was confirmed.
2020-05-26 | GSE144605 | GEO