title: Fluorescein angiography, optical coherence tomography, and histopathologic findings in a VEGF(165) animal model of retinal angiogenesis.
abstract: BACKGROUND
  To establish an animal model of retinal neovascularization using vascular endothelial growth factor (VEGF165) and analyze the model using optical coherence tomography (OCT), fluorescein angiography (FA), and histopathologic evaluation.
  
  
  METHODS
  Twelve rabbits were divided into groups as follows: group 1 (n = 3), sham intravitreous injections of 0.1 ml of balanced saline; group 2 (n = 6), one 10-μg intravitreal injection of VEGF165 on day 0; and group 3 (n = 3), two 10-μg intravitreal injections of VEGF165, one on day 0 and one on day 7. Follow-up evaluations (days 0, 3, 7, 14, 21, 28) included obtaining fundus color photographs and FA, OCT, and histopathologic examinations. Eyes were enucleated and stained with hematoxylin and eosin (H&E).
  
  
  RESULTS
  One injection of VEGF (group 2) was associated with dilatation and tortuosity of the retinal blood vessels that developed within 72 h. Retinal neovascularization was present by day 7 and regressed by day 14. However, even on day 28, the capillaries were still tortuous. Two VEGF injections (group 3) caused increased leakage and neovascularization up to day 14; severe capillary nonperfusion was seen during week 4. At the end of the follow-up period, OCT and histopathologic examination of group 3 showed peripapillary tractional retinal detachments. By day 7, the differences between the retinal thickness seen on OCT in groups 2 and 3 and the group 1 control group were significant (p < 0.001). The histologic findings showed increased vessel size in groups 2 and 3 by days 14 and 28 compared with the controls.
  
  
  CONCLUSIONS
  FA, OCT, and histopathologic findings showed that this retinal neovascularization model is efficient, sustainable, and reliable. One injection of VEGF165 created neovascularization that peaked after 1 week; two injections created more intense neovascularization that evolved to retinal detachments after 4 weeks.
authors.affiliation: Doheny Eye Institute and Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA. aranaoftalmologia@gmail.com
authors.forename: Luís A
authors.initials: LA
authors.lastname: Arana
authors.forename: Anderson T
authors.initials: AT
authors.lastname: Pinto
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Chader
authors.forename: Jose D
authors.initials: JD
authors.lastname: Barbosa
authors.forename: Sabina
authors.initials: S
authors.lastname: Morales
authors.forename: Ana T
authors.initials: AT
authors.lastname: Moreira
authors.forename: Mauricio
authors.initials: M
authors.lastname: Maia
authors.forename: Mark S
authors.initials: MS
authors.lastname: Humayun
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005451:Fluorescein Angiography; D006801:Humans; D058449:Intravitreal Injections; D011817:Rabbits; D011994:Recombinant Proteins; D012163:Retinal Detachment / Q000139:chemically induced / Q000175:diagnosis*; D015861:Retinal Neovascularization / Q000139:chemically induced / Q000175:diagnosis*; D012171:Retinal Vessels / Q000473:pathology*; D041623:Tomography, Optical Coherence; D042461:Vascular Endothelial Growth Factor A
chemical_list: D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A