Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms

• Published in: The Journal of clinical investigation 2002-02, Vol.109 (3), p.327-336
• Main Authors: Stalmans, Ingeborg, Ng, Yin-Shan, Rohan, Richard, Fruttiger, Marcus, Bouché, Ann, Ÿuce, Ali, Fujisawa, Hajime, Hermans, Bart, Shani, Moshe, Jansen, Sandra, Hicklin, Dan, Anderson, David J., Gardiner, Tom, Hammes, Hans-Peter, Moons, Lieve, Dewerchin, Mieke, Collen, Désiré, Carmeliet, Peter, D’Amore, Patricia A.
• Format: Article
• Language: English
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI14362

The murine VEGF gene is alternatively transcribed to yield the VEGF 120 , VEGF 164 , and VEGF 188 isoforms, which differ in their potential to bind to heparan sulfate and neuropilin-1 and to stimulate endothelial growth. Here, their role in retinal vascular development was studied in mice selectively expressing single isoforms. VEGF 164/164 mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF 120/120 mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF 188/188 mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF 164 , was predominantly expressed in retinal arterioles. These findings reveal distinct roles of the various VEGF isoforms in vascular patterning and arterial development in the retina.