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The effect of DOT1L on human retinal microvascular endothelial cells

ABSTRACT: The effect of DOT1L on human retinal microvascular endothelial cells

PROVIDER: PRJNA1271036 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR33798722_1.fastq.gz	Fastqsanger.gz
	SRR33798722_2.fastq.gz	Fastqsanger.gz
	SRR33798723_1.fastq.gz	Fastqsanger.gz
	SRR33798723_2.fastq.gz	Fastqsanger.gz
	SRR33798724_1.fastq.gz	Fastqsanger.gz

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Project description:Retinal neovascularization is a critical component in the pathogenesis of common ocular disorders that cause blindness, and treatment options are limited. We evaluated the therapeutic effect of a DNA enzyme targeting c-jun mRNA in mice with pre-existing retinal neovascularization. A single injection of Dz13 in a lipid formulation containing N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium methyl-sulfate and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine inhibited c-Jun expression and reduced retinal microvascular density. The DNAzyme inhibited retinal microvascular density as effectively as VEGF-A antibodies. Comparative microarray and gene expression analysis determined that Dz13 suppressed not only c-jun but a range of growth factors and matrix-degrading enzymes. Dz13 in this formulation inhibited microvascular endothelial cell proliferation, migration and tubule formation in vitro. Moreover, animals treated with Dz13 sensed the top of the cage in a modified forepaw reach model, unlike mice given a DNAzyme with scrambled RNA-binding arms that did not affect c-Jun expression. These findings demonstrate reduction of microvascular density and improvement in forepaw reach in mice administered catalytic DNA. Total RNA from pooled eyes was used to prepare labeled probes for microarrays. Pooled samples included a Control, Vehicle, Dz13 and Dz13_scrambled.

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