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PLoS One. 2014 Sep 4;9(9):e106507. doi: 10.1371/journal.pone.0106507. eCollection 2014.

Characterization of a spontaneous retinal neovascular mouse model.

Author information

1
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.
2
Schepens Eye Research Institute, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
3
The Jackson Laboratory, Bar Harbor, Maine, United States of America.
4
Angiogenesis Laboratory, Department of Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, Massachusetts, United States of America.
5
Vascular Biology Program, Department of Surgery, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
6
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.
7
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.

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.

PMID:
25188381
PMCID:
PMC4154693
DOI:
10.1371/journal.pone.0106507
[Indexed for MEDLINE]
Free PMC Article

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