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VEGF(164)-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization

Ishida, S; Usui, T; Yamashiro, K; Kaji, Y; Amano, S; Ogura, Y; Hida, T; ... Adamis, AP; + view all (2003) VEGF(164)-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization. J EXP MED , 198 (3) 483 - 489. 10.1084/jem.20022027. Green open access

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Abstract

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF(164) increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF(164)-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF(164)-deficient (VEGF(120/188)) mice exhibited no difference in physiological neovascularization when compared with wild-type (VEGF(+/+)) controls. In contrast, administration of a VEGFk-1/Fc fusion protein, which blocks all VEGF isoforms, led to significant suppression of both pathological and physiological neovascularization. In addition, the targeted inactivation of monocyte lineage cells with clodronate-liposomes led to the suppression of pathological neovascularization. Conversely, the blockade of T lymphocyte-mediated immune responses with an anti-CD2 antibody exacerbated pathological neovascularization. These data highlight important molecular and cellular differences between physiological and pathological retinal neovascularization. During pathological neovascularization, VEGF(164) selectively induces inflammation and cellular immunity. These processes provide positive and negative angiogenic regulation, respectively. Together, new therapeutic approaches for selectively targeting pathological, but not physiological, retinal neovascularization are outlined.

Type: Article
Title: VEGF(164)-mediated inflammation is required for pathological, but not physiological, ischemia-induced retinal neovascularization
Open access status: An open access version is available from UCL Discovery
DOI: 10.1084/jem.20022027
Keywords: retina, angiogenesis, VEGF, leukocyte, immunity, ENDOTHELIAL GROWTH-FACTOR, ADHESION MOLECULE-1 ICAM-1, CELL-ADHESION, FACTOR VEGF, ANGIOGENESIS, RETINOPATHY, EXPRESSION, POTENCY, FLT-1
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/7880
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