title: Angiopoietin-2 enhances retinal vessel sensitivity to vascular endothelial growth factor.
abstract: Increased expression of vascular endothelial growth factor (VEGF) in the retina starting after postnatal day (P)7 results in neovascularization originating from deep retinal capillaries, but not those in the superficial capillary bed. Doxycycline was administered starting P0 to double transgenic mice with inducible expression of VEGF in the retina. These mice showed proliferation and dilation of superficial retinal capillaries, indicating that at this stage of development, the superficial capillaries are sensitive to the effects of VEGF. Angiopoietin-2 (Ang2) is expressed along the surface of the retina for several days after birth, but by P7 and later, Ang2 is only expressed in the region of the deep capillary bed. In mice with ubiquitous doxycycline-inducible expression of Ang2, in the absence of doxycycline, intravitreous injection of a gutless adenoviral vector expressing VEGF (AGV.VEGF) resulted in neovascularization of the cornea and iris, but no retinal neovascularization. After treatment with doxycycline to induce Ang2 expression, intravitreous injection of AGV.VEGF caused retinal neovascularization in addition to corneal and iris neovascularization. The retinal neovascularization originated from both the superficial and deep capillary beds. These data suggest that Ang2 promotes sensitivity to the angiogenic effects of VEGF in retinal vessels.
authors.affiliation: Department of Ophthalmology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Oshima
authors.forename: Tye
authors.initials: T
authors.lastname: Deering
authors.forename: Sachiko
authors.initials: S
authors.lastname: Oshima
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nambu
authors.forename: P Seshidhar
authors.initials: PS
authors.lastname: Reddy
authors.forename: Michael
authors.initials: M
authors.lastname: Kaleko
authors.forename: Sheila
authors.initials: S
authors.lastname: Connelly
authors.forename: Sean F
authors.initials: SF
authors.lastname: Hackett
authors.forename: Peter A
authors.initials: PA
authors.lastname: Campochiaro
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D042702:Angiopoietin-2 / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D005822:Genetic Vectors; D051379:Mice; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic; D012333:RNA, Messenger / Q000032:analysis; D012160:Retina / Q000254:growth & development*; D015861:Retinal Neovascularization; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology
chemical_list: D042702:Angiopoietin-2; D000900:Anti-Bacterial Agents; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D004318:Doxycycline