Characterization of a spontaneous retinal neovascular mouse model

Eiichi Hasegawa, Harry Sweigard, Deeba Husain, Ana M. Olivares, Bo Chang, Kaylee E. Smith, Amy E. Birsner, Robert J. D'Amato, Norman A. Michaud, Yinan Han, Demetrios G. Vavvas, Joan W. Miller, Neena B. Haider, Kip M. Connor

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Article numbere106507
JournalPloS one
Volume9
Issue number9
DOIs
Publication statusPublished - Sep 4 2014
Externally publishedYes

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Retinal Pigments
angiogenesis
Angiography
retina
animal models
Retina
Retinal Pigment Epithelium
Fluorescein
blood vessels
lesions (animal)
Pathologic Neovascularization
epithelium
Fluorescein Angiography
blindness
pigments
mice
Blindness
fluorescein
Confocal microscopy
Optical tomography

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hasegawa, E., Sweigard, H., Husain, D., Olivares, A. M., Chang, B., Smith, K. E., ... Connor, K. M. (2014). Characterization of a spontaneous retinal neovascular mouse model. PloS one, 9(9), [e106507]. https://doi.org/10.1371/journal.pone.0106507

Characterization of a spontaneous retinal neovascular mouse model. / Hasegawa, Eiichi; Sweigard, Harry; Husain, Deeba; Olivares, Ana M.; Chang, Bo; Smith, Kaylee E.; Birsner, Amy E.; D'Amato, Robert J.; Michaud, Norman A.; Han, Yinan; Vavvas, Demetrios G.; Miller, Joan W.; Haider, Neena B.; Connor, Kip M.

In: PloS one, Vol. 9, No. 9, e106507, 04.09.2014.

Research output: Contribution to journalArticle

Hasegawa, E, Sweigard, H, Husain, D, Olivares, AM, Chang, B, Smith, KE, Birsner, AE, D'Amato, RJ, Michaud, NA, Han, Y, Vavvas, DG, Miller, JW, Haider, NB & Connor, KM 2014, 'Characterization of a spontaneous retinal neovascular mouse model', PloS one, vol. 9, no. 9, e106507. https://doi.org/10.1371/journal.pone.0106507
Hasegawa E, Sweigard H, Husain D, Olivares AM, Chang B, Smith KE et al. Characterization of a spontaneous retinal neovascular mouse model. PloS one. 2014 Sep 4;9(9). e106507. https://doi.org/10.1371/journal.pone.0106507
Hasegawa, Eiichi ; Sweigard, Harry ; Husain, Deeba ; Olivares, Ana M. ; Chang, Bo ; Smith, Kaylee E. ; Birsner, Amy E. ; D'Amato, Robert J. ; Michaud, Norman A. ; Han, Yinan ; Vavvas, Demetrios G. ; Miller, Joan W. ; Haider, Neena B. ; Connor, Kip M. / Characterization of a spontaneous retinal neovascular mouse model. In: PloS one. 2014 ; Vol. 9, No. 9.
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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.",
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AU - Birsner, Amy E.

AU - D'Amato, Robert J.

AU - Michaud, Norman A.

AU - Han, Yinan

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N2 - 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.

AB - 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.

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