Dataset Information

Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization.

ABSTRACT:

Purpose

Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1? on ocular NV.

Methods

Conditional HIF-1? knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1? floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. The mice were used for the oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) models.

Results

HIF-1? levels were significantly decreased in the RPE layer of ocular sections and in primary RPE cells from the HIF-1? KO mice. Under normal conditions, the HIF-1? KO mice exhibited no apparent abnormalities in retinal histology or visual function as shown by light microscopy and electroretinogram recording, respectively. The HIF-1? KO mice with OIR showed no significant difference from the wild-type (WT) mice in retinal levels of HIF-1? and VEGF as well as in the number of preretinal neovascular cells. In the laser-induced CNV model, however, the disruption of HIF-1? in the RPE attenuated the over expression of VEGF and the intercellular adhesion molecule 1 (ICAM-1), and reduced vascular leakage and CNV area.

Conclusions

RPE-derived HIF-1? plays a key role in CNV, but not in ischemia-induced retinal NV.

SUBMITTER: Lin M

PROVIDER: S-EPMC4113187 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization.

Lin Mingkai M Hu Yang Y Chen Ying Y Zhou Kevin K KK Jin Ji J Zhu Meili M Le Yun-Zheng YZ Ge Jian J Ma Jian-Xing JX

Investigative ophthalmology & visual science 20120914 10

<h4>Purpose</h4>Hypoxia-inducible factor (HIF)-1 is a key oxygen sensor and is believed to play an important role in neovascularization (NV). The purpose of this study is to determine the role of retinal pigment epithelium (RPE)-derived HIF-1α on ocular NV.<h4>Methods</h4>Conditional HIF-1α knockout (KO) mice were generated by crossing transgenic mice expressing Cre in the RPE with HIF-1α floxed mice, confirmed by immunohistochemistry, Western blot analysis, and fundus fluorescein angiography. T ...[more]

PMID: 22915031

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Project description:Background: To identify and functionally annotate cell type-specific gene expression in the human retinal pigment epithelium (RPE), a key tissue involved in age-related macular degeneration and retinitis pigmentosa. Methodology: RPE, photoreceptor and choroidal cells were isolated from selected freshly frozen healthy human donor eyes using laser microdissection. RNA isolation, amplification and hybridization to 44k microarrays was carried out according to Agilent specifications. Bioinformatics was carried out using Rosetta Resolver, David and Ingenuity software. Principal Findings: Our previous 22k analysis of the RPE transcriptome showed that the RPE has high levels of protein synthesis, strong energy demands, is exposed to high levels of oxidative stress and a variable degree of inflammation. We currently use a complementary new strategy aimed at the identification and functional annotation of RPE-specific expressed transcripts. This strategy takes advantage of the multilayered cellular structure of the retina and overcomes a number of limitations of previous studies. In triplicate, we compared the transcriptomes of RPE, photoreceptor and choroidal cells and we deduced RPE specific expression. We identified at least 114 entries with RPE-specific gene expression. Thirty-nine of these 114 genes also show high expression in the RPE, comparison with the literature showed that 85% of these 39 were previously identified to be expressed in the RPE. In the group of 114 RPE specific genes there was an overrepresentation of genes involved in (membrane) transport, vision and ophthalmic disease. More fundamentally, we found RPE-specific involvement in the RAR-activation, retinol metabolism and GABA receptor signaling pathways. Conclusions: In this study we provide a further specification and understanding of the RPE transcriptome by identifying and analyzing genes that are specifically expressed in the RPE. Six RPE samples, three phot samples, three choroid samples

Dataset Information

Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization.

Purpose

Methods

Results

Conclusions

Publications

Impacts of hypoxia-inducible factor-1 knockout in the retinal pigment epithelium on choroidal neovascularization.

Similar Datasets

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