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Identification of genes and pathways involved in retinal neovascularization by microarray analysis of two animal models of retinal angiogenesis.

ABSTRACT: Comparative retinal gene expression analysis in two rodent models of oxygen-induced retinopathy (OIR) was performed to identify the genes and pathways involved in retinal neovascularization.Three independent experimental runs were conducted for each species, according to standard protocols for induction of OIR. Total retinal RNA was isolated at two time points, corresponding to the early response to relative hypoxia (P13 in mouse, P15 in rat) and to the later phase of maximum retinal neovascularization (P18 in mouse, P20 in rat) and was used to prepare labeled probes for hybridization. Gene expression was compared between normal and experimental conditions for each species at each time point. Probesets with a false-discovery rate of

SUBMITTER: Recchia FM

PROVIDER: S-EPMC2868453 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Identification of genes and pathways involved in retinal neovascularization by microarray analysis of two animal models of retinal angiogenesis.

Recchia Franco M FM Xu Lili L Penn John S JS Boone Braden B Dexheimer Phillip J PJ

Investigative ophthalmology & visual science 20091015 2

<h4>Purpose</h4>Comparative retinal gene expression analysis in two rodent models of oxygen-induced retinopathy (OIR) was performed to identify the genes and pathways involved in retinal neovascularization.<h4>Methods</h4>Three independent experimental runs were conducted for each species, according to standard protocols for induction of OIR. Total retinal RNA was isolated at two time points, corresponding to the early response to relative hypoxia (P13 in mouse, P15 in rat) and to the later phas ...[more]

PMID: 19834031

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Project description:BackgroundNeovascularization is an important repair mechanism in response to ischemic injury and is dependent on inflammation, angiogenesis and reactive oxygen species (ROS). IQGAP1, an actin-binding scaffold protein, is a key regulator for actin cytoskeleton and motility. We previously demonstrated that IQGAP1 mediates vascular endothelial growth factor (VEGF)-induced ROS production and migration of cultured endothelial cells (ECs); however, its role in post-ischemic neovascularization is unknown.Methodology/principal findingsIschemia was induced by left femoral artery ligation, which resulted in increased IQGAP1 expression in Mac3(+) macrophages and CD31(+) capillary-like ECs in ischemic legs. Mice lacking IQGAP1 exhibited a significant reduction in the post-ischemic neovascularization as evaluated by laser Doppler blood flow, capillary density and ?-actin positive arterioles. Furthermore, IQGAP1(-/-) mice showed a decrease in macrophage infiltration and ROS production in ischemic muscles, leading to impaired muscle regeneration and increased necrosis and fibrosis. The numbers of bone marrow (BM)-derived cells in the peripheral blood were not affected in these knockout mice. BM transplantation revealed that IQGAP1 expressed in both BM-derived cells and tissue resident cells, such as ECs, is required for post-ischemic neovascularization. Moreover, thioglycollate-induced peritoneal macrophage recruitment and ROS production were inhibited in IQGAP1(-/-) mice. In vitro, IQGAP1(-/-) BM-derived macrophages showed inhibition of migration and adhesion capacity, which may explain the defective macrophage recruitment into the ischemic tissue in IQGAP1(-/-) mice.Conclusions/significanceIQGAP1 plays a key role in post-ischemic neovascularization by regulating, not only, ECs-mediated angiogenesis but also macrophage infiltration as well as ROS production. Thus, IQGAP1 is a potential therapeutic target for inflammation- and angiogenesis-dependent ischemic cardiovascular diseases.

Dataset Information

Identification of genes and pathways involved in retinal neovascularization by microarray analysis of two animal models of retinal angiogenesis.

Publications

Identification of genes and pathways involved in retinal neovascularization by microarray analysis of two animal models of retinal angiogenesis.

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