title: Characterization of a spontaneous retinal neovascular mouse model.
abstract: BACKGROUND
  Vision loss due to vascular disease of the retina is a leading cause of blindness in the world. Retinal angiomatous proliferation (RAP) is a subgroup of neovascular age-related macular degeneration (AMD), whereby abnormal blood vessels develop in the retina leading to debilitating vision loss and eventual blindness. The novel mouse strain, neoretinal vascularization 2 (NRV2), shows spontaneous fundus changes associated with abnormal neovascularization. The purpose of this study is to characterize the induction of pathologic angiogenesis in this mouse model.
  
  
  METHODS
  The NRV2 mice were examined from postnatal day 12 (p12) to 3 months. The phenotypic changes within the retina were evaluated by fundus photography, fluorescein angiography, optical coherence tomography, and immunohistochemical and electron microscopic analysis. The pathological neovascularization was imaged by confocal microscopy and reconstructed using three-dimensional image analysis software.
  
  
  RESULTS
  We found that NRV2 mice develop multifocal retinal depigmentation in the posterior fundus. Depigmented lesions developed vascular leakage observed by fluorescein angiography. The spontaneous angiogenesis arose from the retinal vascular plexus at postnatal day (p)15 and extended toward retinal pigment epithelium (RPE). By three months of age, histological analysis revealed encapsulation of the neovascular lesion by the RPE in the photoreceptor cell layer and subretinal space.
  
  
  CONCLUSIONS
  The NRV2 mouse strain develops early neovascular lesions within the retina, which grow downward towards the RPE beginning at p15. This retinal neovascularization model mimics early stages of human retinal angiomatous proliferation (RAP) and will likely be a useful in elucidating targeted therapeutics for patients with ocular neovascular disease.
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Hasegawa
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Harry
authors.initials: H
authors.lastname: Sweigard
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Deeba
authors.initials: D
authors.lastname: Husain
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Olivares
authors.affiliation: The Jackson Laboratory, Bar Harbor, Maine, United States of America.
authors.forename: Bo
authors.initials: B
authors.lastname: Chang
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Kaylee E
authors.initials: KE
authors.lastname: Smith
authors.affiliation: Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Birsner
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America; Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: D'Amato
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Norman A
authors.initials: NA
authors.lastname: Michaud
authors.affiliation: Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Han
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Demetrios G
authors.initials: DG
authors.lastname: Vavvas
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Miller
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America; Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
authors.forename: Neena B
authors.initials: NB
authors.lastname: Haider
authors.affiliation: Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America; Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts, United States of America.
authors.forename: Kip M
authors.initials: KM
authors.lastname: Connor
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005451:Fluorescein Angiography; D008137:Longitudinal Studies; D051379:Mice; D010857:Pigment Epithelium of Eye / Q000473:pathology; D012160:Retina / Q000473:pathology; D015861:Retinal Neovascularization / Q000473:pathology*; D041623:Tomography, Optical Coherence