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Arteriolar and venular patterning in retinas of mice selectively expressing VEGF isoforms
Ingeborg Stalmans, Yin-Shan Ng, Richard Rohan, Marcus Fruttiger, Ann Bouché, Ali Ÿuce, Hajime Fujisawa, Bart Hermans, Moshe Shani, Sandra Jansen, Dan Hicklin, David J. Anderson, Tom Gardiner, Hans-Peter Hammes, Lieve Moons, Mieke Dewerchin, Désiré Collen, Peter Carmeliet, Patricia A. D’Amore
Ingeborg Stalmans, Yin-Shan Ng, Richard Rohan, Marcus Fruttiger, Ann Bouché, Ali Ÿuce, Hajime Fujisawa, Bart Hermans, Moshe Shani, Sandra Jansen, Dan Hicklin, David J. Anderson, Tom Gardiner, Hans-Peter Hammes, Lieve Moons, Mieke Dewerchin, Désiré Collen, Peter Carmeliet, Patricia A. D’Amore
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Article

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

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Abstract

The murine VEGF gene is alternatively transcribed to yield the VEGF120, VEGF164, and VEGF188 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. VEGF164/164 mice were normal, healthy, and had normal retinal angiogenesis. In contrast, VEGF120/120 mice exhibited severe defects in vascular outgrowth and patterning, whereas VEGF188/188 mice displayed normal venular outgrowth but impaired arterial development. It is noteworthy that neuropilin-1, a receptor for VEGF164, 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.

Authors

Ingeborg Stalmans, Yin-Shan Ng, Richard Rohan, Marcus Fruttiger, Ann Bouché, Ali Ÿuce, Hajime Fujisawa, Bart Hermans, Moshe Shani, Sandra Jansen, Dan Hicklin, David J. Anderson, Tom Gardiner, Hans-Peter Hammes, Lieve Moons, Mieke Dewerchin, Désiré Collen, Peter Carmeliet, Patricia A. D’Amore

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Figure 3

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Retinal vascular development in VEGF188/188 mice. (a) PECAM staining at ...
Retinal vascular development in VEGF188/188 mice. (a) PECAM staining at P5. Capillary outgrowth comparable to VEGF+/+ retinas, but no morphologically defined arterioles. (b and c) EB2/CollIV at P5. No EB2 expression at P5. Inset in c: VEGF188/188 × EB2LacZ retina at P6 shows small ephrin-B2–positive vessel (arrow). (d and e) LacZ/Lec/SMA on a VEGF188/188 × PECLacZ retina at P5, revealing (b) high PC density, (c) but no SMA immunoreactivity. (f) EM at P5 shows normal capillary constriction. (g) PECAM staining at P9 with increased capillary density in the midperipheral retina (arrow) and partially removed hyaloid arteries. (h) SMA immunoreactivity is attenuated in arterioles, but has become positive in venules and capillaries (arrow) at P14. (i and j) VEGF188/188 × PECLacZ retina at 4 weeks. (i) Persistence of hyaloid arteries and underdevelopment of arterioles. (j) Same retina after dissection of hyaloid arteries. Central part, but not peripheral part (arrows), of hyaloid arteries can be removed. (k) Lec/GFAP. ACs are organized into a tubular network well in front of the vascular bed.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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