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 VEGF(120) 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.
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 humandonor 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 VEGF(120) 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.
Authors: Jingtai Cao; Lian Zhao; Yiwen Li; Yang Liu; Weihong Xiao; Ying Song; Lingyu Luo; Deqiang Huang; George D Yancopoulos; Stanley J Wiegand; Rong Wen Journal: Invest Ophthalmol Vis Sci Date: 2010-06-10 Impact factor: 4.799
Authors: Maud Jost; Catherine Maillard; Julie Lecomte; Vincent Lambert; Marc Tjwa; Pierre Blaise; Maria-Luz Alvarez Gonzalez; Khalid Bajou; Silvia Blacher; Patrick Motte; Chantal Humblet; Marie Paule Defresne; Marc Thiry; Francis Frankenne; André Gothot; Peter Carmeliet; Jean-Marie Rakic; Jean-Michel Foidart; Agnès Noël Journal: Am J Pathol Date: 2007-08-23 Impact factor: 4.307