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Placental Growth Factor, a Member of the VEGF Family, Contributes to the Development of Choroidal Neovascularization

¹From the Department of Ophthalmology, University Hospital, Sart-Tilman, Liège, Belgium; the ²Laboratory of Tumor and Development Biology and the ⁵Center for Cellular and Molecular Neurobiology, University of Liège, Liège, Belgium; the ³Center for Transgene Technology and Gene Therapy, Katholieke Universiteit Leuven, Leuven, Belgium; and the ⁴Department of Ophthalmology, Middelheim Hospital, Antwerpen, Belgium.

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 (PlGF), 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 PlGF mRNA expression were explored by using the laser capture catapulting technique and RT-PCR in a murine laser-induced model and in vitro. PlGF expression was also studied in human donor eyes. The influence of endogenous PlGF was evaluated in deficient mice (PlGF^-/-) and by antibody-mediated neutralization of the PlGF receptor.

RESULTS. Human neovascular membranes consistently expressed VEGF-A, -B, and -C; PlGF; and VEGFR-1 and -2. The VEGF₁₂₀ isoform mRNA was primarily induced in early stages of angiogenesis in vivo and in vitro. PlGF mRNA expression was present in the intact choroid and significantly upregulated during the course of experimental CNV. Both deficient PlGF expression in PlGF^-/- mice and PlGF receptor neutralization in wild-type mice prevented the development of choroidal neovascularization induced by laser.

CONCLUSIONS. These observations demonstrate the participation of PlGF in experimental CNV. They identify therefore PlGF as an additional promising target for ocular antiangiogenic strategies.

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