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COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

ABSTRACT: COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

PROVIDER: PRJNA671828 | ENA |

REPOSITORIES: ENA

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COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

Project description:Neovascularization contributes to multiple visual disorders including age-related macular degeneration (AMD). Current therapies for treating ocular angiogenesis are centered on the inhibition of vascular endothelial growth factor (VEGF). While clinically effective, some AMD patients are refractory or develop resistance to anti-VEGF and concerns of increased risks of developing geographic atrophy following long-term treatment have been raised. Identification of alternative pathways to inhibit pathological angiogenesis is thus important. We have identified a novel inhibitor of angiogenesis, COCO/DAND5, a member of the Cerberus-related DAN family. We demonstrate that COCO inhibits sprouting, migration and cellular proliferation of cultured endothelial cells. Intravitreal injections of COCO inhibited retinal vascularization during development and in models of retinopathy of prematurity and AMD. COCO equally abrogated angiogenesis in choroid explants and in a model of choroidal neovascularization. Mechanistically, COCO inhibited the expression of TGFβ and BMP pathwaysand altered ATP production, glucose uptake and redox balance of endothelial cells. Together, these data show that COCO is an inhibitor of retinal and choroidal angiogenesis, possibly representing a therapeutic option for the treatment of neovascular ocular diseases.

2020-12-22 | GSE160099 | GEO

COCO/DAND5 inhibits developmental and pathological ocular angiogenesis.

Project description: Not available

| S-EPMC7933934 | biostudies-literature

COCO/DAND5 inhibits developmental and pathological ocular angiogenesis

Project description: Not available

| S-SCDT-EMM-2020-12005 | biostudies-other

AnxA1 inhibits pathological bone resorption

Project description:AnxA1 inhibits pathological bone resorption

| PRJNA759264 | ENA

Single-cell Transcriptome Analyses Reveal Unique Microglia Types Associated with Retinal Pathological Angiogenesis

Project description:We used single cell RNA-seq to comprehensively map all retinal microglia populations in a mouse model of oxygen-induced PR. We unveiled several unique types of PR-associated microglia (PRAM) and identified markers, signaling pathways, and regulons associated with these cells. Among these microglial subpopulations, we found a highly proliferative subset of cells with a high self-renewal capacity and a subset of cells with hypermetabolism that expresses high levels of activating microglia markers, glycolytic enzymes, and pro-angiogenic insulin-like growth factor 1. Immunohistochemical staining shows that PRAMs were spatially located within neovascular tufts. These unique microglial subtypes have the potential to promote retinal angiogenesis, which may have important implications for the future treatment of PR and other ocular diseases characterized by pathological angiogenesis.

2023-01-17 | GSE199792 | GEO

Oxygen-induced pathological angiogenesis promotes intense lipid synthesis and remodeling in the retina

Project description:<p>The retina is a notable tissue with high metabolic needs which relies on specialized vascular networks to protect the neural retina while maintaining constant supplies of oxygen, nutrients and dietary essential fatty acids. Here we analyzed the lipidome of the mouse retina under healthy and pathological angiogenesis using the oxygen-induced retinopathy model. By matching lipid profiles to changes in mRNA transcriptome, we identified a lipid signature showing that pathological angiogenesis leads to intense lipid remodeling favoring pathways for neutral lipid synthesis, cholesterol import/export and lipid droplet formation. Noteworthy, it also shows profound changes in pathways for long-chain fatty acid production, vital for retina homeostasis. The net result is accumulation of large quantities of mead acid, a marker of essential fatty acid deficiency, and a potential marker for retinopathy severity. Thus, our lipid signature might contribute to better understand diseases of the retina that lead to vision impairment or blindness.</p>

2023-05-09 | MTBLS6965 | MetaboLights

Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis.

Project description: Not available

| S-EPMC5264653 | biostudies-literature

Identifying the origin and mechanisms of pathological angiogenesis in neuroinflammatory diseases

Project description:Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). Studies in human MS and its animal model experimental autoimmune encephalomyelitis (EAE) have shown that new abnormal vessels develop in demyelinating plaques through pathological neo-angiogenesis, which exacerbates MS/EAE pathology by contributing to the leakage of serum components and infiltration of immune cells into the CNS. However, the cellular origin and the signaling pathways underlying this pathology remain poorly understood. Here, using single-cell RNA sequencing and validation with in situ hybridization and immunofluorescence, we discovered that neo-angiogenesis is initiated specifically by venous endothelial cells during EAE. Moreover, we identified VEGF-A signaling as the primary driver of neo-angiogenesis in EAE, as treatment with the VEGF-A blocking antibody, bevacizumab, ameliorated the EAE pathology by reducing neo-angiogenesis in vivo. Our findings may lead to the development of novel therapeutics designed to reduce neo-angiogenesis and improve long-term neurological deficits in MS.

2023-03-14 | GSE210776 | GEO

Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

Project description:Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

| PRJEB35871 | ENA

Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

Project description:Endothelial cell heterogeneity in pathological angiogenesis characterized by metabolic transcriptome diversity

| PRJEB52990 | ENA