title: Different effects of angiopoietin-2 in different vascular beds: new vessels are most sensitive.
abstract: In this study, we used double transgenic mice with inducible expression of angiopoietin-2 (Ang2) to investigate the role of Ang2 in the retinal and choroidal circulations and in three models of ocular neovascularization (NV). Mice with induced expression of Ang2 ubiquitously, or specifically in the retina, survived and appeared grossly normal. They also had normal-appearing retinal and choroidal circulations, demonstrating that high levels of Ang2 did not induce regression of mature retinal or choroidal vessels. When Ang2 expression was induced soon after birth, there was increased density of the deep capillary bed on postnatal day (P) 11 that returned to normal by P18, the time that retinal vascular development is usually completed. In mice with ischemic retinopathy, induction of Ang2 during the ischemic period resulted in a significant increase in retinal NV, but induction of Ang2 at a later time point when ischemia (and vascular endothelial growth factor [VEGF]) was less, hastened regression of NV. In triple transgenic mice that coexpressed VEGF and Ang2, the increased expression of Ang2 inhibited VEGF-induced NV in the retina. Increased expression of Ang2 also resulted in regression of choroidal neovascularization. These data suggest that ocular neovascularization, but not mature retinal or choroidal vessels, is sensitive to Ang2; a high Ang2/VEGF ratio promotes regression, while high Ang2 in the setting of hypoxia and/or concomitantly high Ang2 and VEGF stimulate neovascularization.
authors.affiliation: Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-9277, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oshima
authors.forename: Sachiko
authors.initials: S
authors.lastname: Oshima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nambu
authors.forename: Shu
authors.initials: S
authors.lastname: Kachi
authors.forename: Kyoichi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Naoyasu
authors.initials: N
authors.lastname: Umeda
authors.forename: JiKui
authors.initials: J
authors.lastname: Shen
authors.forename: Aling
authors.initials: A
authors.lastname: Dong
authors.forename: Rajendra S
authors.initials: RS
authors.lastname: Apte
authors.forename: Elia
authors.initials: E
authors.lastname: Duh
authors.forename: Sean F
authors.initials: SF
authors.lastname: Hackett
authors.forename: Godwin
authors.initials: G
authors.lastname: Okoye
authors.forename: Kazuki
authors.initials: K
authors.lastname: Ishibashi
authors.forename: James
authors.initials: J
authors.lastname: Handa
authors.forename: Michele
authors.initials: M
authors.lastname: Melia
authors.forename: Stanley
authors.initials: S
authors.lastname: Wiegand
authors.forename: George
authors.initials: G
authors.lastname: Yancopoulos
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Zack
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D042702:Angiopoietin-2 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001808:Blood Vessels / Q000254:growth & development*; D002196:Capillaries / Q000254:growth & development; D002829:Choroid / Q000098:blood supply; D004318:Doxycycline / Q000008:administration & dosage; D015870:Gene Expression; D007511:Ischemia / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D010786:Photoreceptor Cells / Q000737:chemistry; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000737:chemistry; D012171:Retinal Vessels / Q000254:growth & development / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012243:Rhodopsin / Q000235:genetics / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000494:pharmacology / Q000502:physiology
chemical_list: D042702:Angiopoietin-2; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D012243:Rhodopsin; D004318:Doxycycline