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Dopamine D2 receptor activation inhibits choroidal neovascularization in Parkinson patients with age related macular degeneration.

ABSTRACT: Dopamine D2 receptor activation inhibits choroidal neovascularization in Parkinson patients with age related macular degeneration.

PROVIDER: PRJNA1107506 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR28890629_1.fastq.gz	Fastqsanger.gz
	SRR28890629_2.fastq.gz	Fastqsanger.gz
	SRR28890630_1.fastq.gz	Fastqsanger.gz
	SRR28890630_2.fastq.gz	Fastqsanger.gz
	SRR28890631_1.fastq.gz	Fastqsanger.gz

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Dopamine D2 receptor activation inhibits choroidal neovascularization in Parkinson patients with age related macular degeneration.

Project description:Neovascular age-related macular degeneration (nAMD) remains a major cause of visual impairment and puts considerable burden on patients and health care systems. L-DOPA-treated Parkinson Disease (PD) patients have been shown to be partially protected from nAMD, but the mechanism remains unknown. Using murine models combining 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD and laser-induced nAMD, standard PD treatment of L-DOPA/DOPA-decarboxylase inhibitor, or specific dopamine receptor inhibitors, we here demonstrate that L-DOPA treatment-induced increase of dopamine receptor D2 (DRD2) signaling inhibits choroidal neovascularization independently of MPTP-associated nigrostriatal pathway lesion. Analyzing a retrospective cohort of more than two hundred thousand nAMD patients receiving anti-VEGF treatment from the French nationwide insurance database, we show that DRD2-agonist treated (PD) patients have a significantly delayed age of onset for nAMD (81.4 (±7.0) vs 79.4 (±8.1) years old, respectively, p<0.0001) and reduced need for anti-VEGF therapies (-0.6 injections per 100 mg/day daily dose of DRD2 agonists the second year of treatment), similar to the L-DOPA treatment. While providing a mechanistic explanation for an intriguing epidemiological observation, our findings suggest that systemic DRD2 agonists might constitute an adjuvant therapy to delay and reduce the need for anti-VEGF therapy in nAMD patients.

2024-09-13 | GSE266525 | GEO

RNA analysis of the circadian rhythm of choroidal neovascularization

Project description:Many diseases that affect the heart, brain, and even the eyes originate from vascular pathology, emphasizing the role of vascular regulation. In age-related macular degeneration (AMD), excessive growth of abnormal blood vessels in the eye (choroidal neovascularization) ultimately leads to detachment of retinal pigment epithelium and decreased vision, indicating the importance of choroidal neovascularization in the treatment of age-related diseases. The circadian clock in the mammalian retina regulates various retinal functions, enabling the retina to adapt to the light dark cycle. Emerging evidence suggests a link between circadian clock and retinopathy, but the causal relationship has not yet been determined.

2024-10-09 | GSE253949 | GEO

Expression profiles of long non-coding RNAs and messenger RNAs in laser-induced choroidal neovascularization in mice.

Project description:Choroidal neovascularization (CNV) is a severe complication of the late-stage form of wet age-related macular degeneration. In order to identify lncRNAs and coding genes involved in the pathogenesis of CNV, we performed microarray analysis to identify expression profiles of lncRNAs and mRNAs in laser-induced CNV samples and controls in mice.

2019-04-13 | GSE129743 | GEO

RNA-seq of choroid and retina in tree shrews with choroidal neovascularization

Project description:In order elucidate the key signaling pathways in choroidal neovascularization, we induced choroidal angiogenesis by laser photocoagulation in 12 tree shrews and obtained mRNA profiles of their choroids and retinas by high-throughput transcriptome sequencing. Gene ontology(GO) and kyoto encyclopedia of genes and genomes(KEGG) enrichment analysis, hierarchical cluster analysis, weighted gene co-expression network analysis, protein-protein interaction (PPI) network analysis, and reverse transcription quantitative PCR (RT-qPCR) were performed.

2021-03-21 | E-MTAB-10198 | biostudies-arrayexpress

tRF/tiRNA expression profile of RPE-choroid-sclera complex in the laser-induced choroidal neovascularization mouse model

Project description:To investigate the tRF/tiRNA expression pattern in the development of choroidal neovascularization, we built a laser-induced choroidal neovascularization mouse model and performed the tRF/tiRNA sequencing on RPE-choroid-sclera complexes at different time points after model establishment, while the tissues from mice without treatment were used as control group.

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Expression profiles of microRNAs and transfer RNA-derived small RNAs in laser-induced choroidal neovascularization in mice.

Project description:The purpose of the study was to investigate the roles and possible functions of the miRNAs and tsRNAs in choroidal neovascularization (CNV).The mouse model of laser-induced CNV was conducted by laser photocoagulation and the samples were collected 7 days after laser treatment. The expression profiles of miRNAs and tsRNAs were accessed by small RNA sequencing in RPE-choroid-sclera complexes of mice in CNV group and controls. Our study identified differential expressions of miRNAs and tsRNAs in CNV model, and these altered miRNAs and tsRNAs might be novel potential targets in treating CNVs in patients with neovascular age-related macular degeneration.

2019-05-23 | GSE131646 | GEO

Expression profile of circRNAs in a mouse model of laser-induced choroidal neovascularization

Project description:To identify the circRNA expression profile in laser-induced choroidal neovascularization (CNV) and controls in mice, we used circRNA microarray analysis to examine the expression of circRNAs in RPE-choroid-sclera complexes of CNV and control mice.

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Secreted phosphoprotein 1 expression in retinal mononuclear phagocytes links murine to human choroidal neovascularization

Project description:Neovascular age-related macular degeneration represents the most common cause of blindness in the western world. Alterations of the outer Blood-retina barrier integrity and a localized inflammatory microenvironment lead to sprouting of choroidal neovascularization in intimate contact with surrounding myeloid cells and ultimately lead to visual impairment. The discovery of novel targets interfering with angiogenesis and inflammation is vital for the future treatments in AMD patients. To identify novel potential targets in the local phagocytes of the retina, microglia, we performed a comprehensive RNA-seq analysis in the mouse model of laser-induced choroidal neovascularization (mCNV). Here, we identified the angiogenic factor Osteopontin (Opn), also known as "secreted phosphoprotein 1” (Spp1), to be one of the most highly expressed genes in retinal microglia in the course of CNV formation. We could confirm the presence of SPP1 at the lesion site in recruited retinal microglia of Cx3cr1CreER:Rosa26-Tomato reporter mice using immunohistochemistry and in whole retinal tissue lysates by ELISA compared to controls highlighting a massive local production of SPP1. Inhibition of SPP1 by intravitreal injection of anti-SPP1 antibody significantly increased the lesion size compared to IgG-treated control eyes. In line with the results in rodents, we found an increased SPP1 mRNA expression in surgically extracted human choroidal neovascular (hCNV) membranes by the quantitative RNA-seq approach of massive analysis of cDNA ends (MACE) and found numerous IBA1+SPP1+ myeloid cells in human CNV membranes. Taken together, these results highlight the importance of SPP1 in the formation of CNV and potentially offer new opportunities for therapeutic intervention by inhibiting the SPP1 pathway.

2021-02-16 | GSE160011 | GEO

Aqueous microRNA profiling in age-related macular degeneration and polypoidal choroidal vasculopathy by next-generation sequencing

Project description:To investigate the roles of microRNAs in the aqueous humor of patients with typical age-related macular degeneration and polypoidal choroidal vasculopathy using next-generation sequencing.

2022-12-29 | GSE221905 | GEO

RNA analysis of the circadian rhythm of choroidal neovascularization

Project description:RNA analysis of the circadian rhythm of choroidal neovascularization

| PRJNA1067979 | ENA