VEGF and KDR gene expression during human embryonic and fetal eye development.
OBJECTIVE
It is important to understand the development of the normal retinal vascular system, because it may provide clues for understanding the mechanisms underlying the neovascularization associated with several retinopathies of infancy and adulthood. However, little is known about normal human ocular vascularization. VEGF is a key growth factor during vascular development and one of its receptors, KDR, plays a pivotal role in endothelial cell proliferation and differentiation. The purpose of this study was to analyze VEGF and KDR gene expression patterns during the development of the human eye during the embryonic and fetal stages.


METHODS
The gene expression of VEGF and KDR was analyzed by in situ hybridization in 7-week-old embryos and in 10- and 18-week-old fetuses. In addition, we performed VEGF and KDR immunohistochemistry experiments on 18-week-old fetus tissue sections.


RESULTS
These results clearly demonstrated that the levels of VEGF and KDR transcripts are correlated during the normal development of the ocular vasculature in humans. The complementarity between the patterns of VEGF and KDR during the early stages of development suggests that VEGF-KDR interactions play a major role in the formation and regression of the hyaloid vascular system (HVS) and in the development of the choriocapillaris. In later stages (i.e., 18-weeks-old fetuses), the expression of KDR seems to be linked to the development of the retinal vascular system. VEGF and KDR transcripts were unexpectedly detected in some nonvascular tissues-that is, in the cornea and in the retina before the development of the retinal vascular system.


CONCLUSIONS
The expression of VEGF and KDR correlates highly with the normal ocular vascularization in humans, but VEGF may also be necessary for nonvascular retinal developmental functions, especially for the coordination of neural retinal development and the preliminary steps of the establishment of the definitive stable retinal vasculature.
Gogat
Karïn
K
Centre de Recherches Thérapeutiques en Ophtalmologie, Equipe d'accueil du Ministère de la Recherche et de l'Enseignement Supérieur No. 2502, Faculté de Médecine Necker, Université René Descartes Paris V, Paris, France.
Le Gat
Laurence
L
Van Den Berghe
Loïc
L
Marchant
Dominique
D
Kobetz
Alexandra
A
Gadin
Stéphanie
S
Gasser
Bernard
B
Quéré
Isabelle
I
Abitbol
Marc
M
Menasche
Maurice
M
D000911:Antibodies, Monoclonal; D017931:DNA Primers / Q000737:chemistry; D015342:DNA Probes; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005123:Eye / Q000098:blood supply / Q000196:embryology* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D018919:Neovascularization, Physiologic / Q000502:physiology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics*
D000911:Antibodies, Monoclonal; D017931:DNA Primers; D015342:DNA Probes; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2