[en] PURPOSE. VEGF has been shown to be necessary, but not sufficient alone, for the development of subretinal pathologic angiogenesis. In the current study, the influence of placental growth factor (PIGF), a member of the VEGF family, in human and experimental choroidal neovascularization (CNV) was investigated. METHODS. The presence of VEGF family member mRNA was evaluated by RT-PCR in neovascular membranes extracted during surgery. The spatial and temporal pattern of VEGF isoforms and PIGF mRNA expression were explored by using the laser capture catapulting technique and RT-PCR in a murine laser-induced model and in vitro. PIGF expression was also studied in human donor eyes. The influence of endogenous PIGF was evaluated in deficient mice (PlGF(-/-)) and by antibody-mediated neutralization of the PIGF receptor. RESULTS. Human neovascular membranes consistently expressed VEGF-A, -B, and -C; PlGF; and VEGFR-1 and -2. The VEGF(120) isoform mRNA was primarily induced in early stages of angiogenesis in vivo and in vitro. PIGF mRNA expression was present in the intact choroid and significantly upregulated during the course of experimental CNV. Both deficient PIGF expression in PIGF(-/-) mice and PIGF receptor neutralization in wild-type mice prevented the development of choroidal neovascularization induced by laser. CONCLUSIONS. These observations demonstrate the participation of PIGF in experimental CNV. They identify therefore PIGF as an additional promising target for ocular antiangiogenic strategies.
Disciplines :
Ophthalmology
Author, co-author :
Rakic, Jean-Marie ; Université de Liège - ULiège > Département des sciences cliniques > Ophtalmologie
Lambert, Vincent ; Centre Hospitalier Universitaire de Liège - CHU > Ophtalmologie
Devy, Laetitia
Luttun, Aernout
Carmeliet, Peter
Claes, Carel
Nguyen, Laurent ; Université de Liège - ULiège > Département des sciences cliniques > Neurologie
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Munaut, Carine ; Université de Liège - ULiège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Language :
English
Title :
Placental growth factor, a member of the VEGF family, contributes to the development of choroidal neovascularization
Publication date :
July 2003
Journal title :
Investigative Ophthalmology and Visual Science
ISSN :
0146-0404
eISSN :
1552-5783
Publisher :
Assoc Research Vision Ophthalmology Inc, Bethesda, United States - Maryland
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