Angiopoietin 1 prevents retinal detachment in an aggressive model of proliferative retinopathy, but has no effect on established neovascularization.
Vascular endothelial growth factor (VEGF) plays a central role in vasoproliferative diseases in the retina, however, other gene products modulate its effects. The angiopoietins are particularly important in this regard. Angiopoietin 2 (Ang2) collaborates with VEGF to stimulate neovascularization (NV) in some situations, but in other situations causes regression of NV. Ang2 also causes a transient increase in vascular density during retinal vascular development. In this study, we sought to determine if Ang1 has similar activities. The effects of Ang1 were tested in double transgenic mice with inducible expression of Ang1. Increased expression of Ang1 in the retina during retinal vascular development did not cause a detectable alteration in vascular density. Also, unlike Ang2, increased expression of Ang1 had no effect on established retinal or choroidal NV. However, when Ang1 expression was initiated simultaneously with that of VEGF, it strongly suppressed VEGF-induced NV and prevented retinal detachment. These data indicate that the timing of Ang1 expression is a critical determinate of its effects on VEGF-induced NV in the retina; it effectively blocks the initiation and progression of NV, but cannot reverse established NV or reduce leakage from NV. These data suggest that increased expression of Ang1 may be a good strategy for prophylaxis of retinal NV, but is unlikely to be effective as monotherapy of established NV.
Nambu
Hiroyuki
H
The Departments of Ophthalmology and Neuroscience, The Johns Hopkins University School of Medicine, Maumenee, Baltimore, Maryland, USA.
Umeda
Naoyasu
N
Kachi
Shu
S
Oshima
Yuji
Y
Akiyama
Hideo
H
Nambu
Rie
R
Campochiaro
Peter A
PA
D042683:Angiopoietin-1 / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D000900:Anti-Bacterial Agents; D003587:Cytomegalovirus / Q000235:genetics; D004195:Disease Models, Animal; D004318:Doxycycline; D015870:Gene Expression / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D012163:Retinal Detachment / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D012171:Retinal Vessels / Q000473:pathology / Q000503:physiopathology*; D017299:Rod Opsins / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
D042683:Angiopoietin-1; D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D017299:Rod Opsins; D042461:Vascular Endothelial Growth Factor A; D004318:Doxycycline