Characterization of a spontaneous retinal neovascular mouse model
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 ev...
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| Veröffentlicht in: | PloS one 2014-09, Vol.9 (9), p.e106507-e106507 |
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| creator | 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 |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1371/journal.pone.0106507 |
| format | Article |
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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.
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.
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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0106507</identifier><identifier>PMID: 25188381</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Angiogenesis ; Angiography ; Animals ; Biology and Life Sciences ; Blindness ; Blood vessels ; Chemical properties ; Confocal microscopy ; Diabetic retinopathy ; Disease ; Disease Models, Animal ; Edema ; Enzyme-Linked Immunosorbent Assay ; Epithelium ; Fluorescein ; Fluorescein Angiography ; Image analysis ; Image processing ; Image reconstruction ; Laboratories ; Lesions ; Longitudinal Studies ; Macular degeneration ; Medical schools ; Medicine and Health Sciences ; Mice ; Microscopic analysis ; Microscopy ; Optical Coherence Tomography ; Photography ; Photoreceptors ; Physicians ; Pigment Epithelium of Eye - pathology ; Research and Analysis Methods ; Retina ; Retina - pathology ; Retinal Neovascularization - pathology ; Retinal pigment epithelium ; Three dimensional analysis ; Tomography, Optical Coherence ; Vascular diseases ; Vascular endothelial growth factor ; Vascularization ; Vision</subject><ispartof>PloS one, 2014-09, Vol.9 (9), p.e106507-e106507</ispartof><rights>COPYRIGHT 2014 Public Library of Science</rights><rights>2014 Hasegawa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2014 Hasegawa et al 2014 Hasegawa et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-d6b6b2e7ad81021f07e94ec7a5a6bdd0d9fcf34721aa10739bd9484322cf5df3</citedby><cites>FETCH-LOGICAL-c758t-d6b6b2e7ad81021f07e94ec7a5a6bdd0d9fcf34721aa10739bd9484322cf5df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154693/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154693/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25188381$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hasegawa, Eiichi</creatorcontrib><creatorcontrib>Sweigard, Harry</creatorcontrib><creatorcontrib>Husain, Deeba</creatorcontrib><creatorcontrib>Olivares, Ana M</creatorcontrib><creatorcontrib>Chang, Bo</creatorcontrib><creatorcontrib>Smith, Kaylee E</creatorcontrib><creatorcontrib>Birsner, Amy E</creatorcontrib><creatorcontrib>D'Amato, Robert J</creatorcontrib><creatorcontrib>Michaud, Norman A</creatorcontrib><creatorcontrib>Han, Yinan</creatorcontrib><creatorcontrib>Vavvas, Demetrios G</creatorcontrib><creatorcontrib>Miller, Joan W</creatorcontrib><creatorcontrib>Haider, Neena B</creatorcontrib><creatorcontrib>Connor, Kip M</creatorcontrib><title>Characterization of a spontaneous retinal neovascular mouse model</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>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.
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.
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.
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.</description><subject>Age</subject><subject>Angiogenesis</subject><subject>Angiography</subject><subject>Animals</subject><subject>Biology and Life Sciences</subject><subject>Blindness</subject><subject>Blood vessels</subject><subject>Chemical properties</subject><subject>Confocal microscopy</subject><subject>Diabetic retinopathy</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Edema</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Epithelium</subject><subject>Fluorescein</subject><subject>Fluorescein Angiography</subject><subject>Image analysis</subject><subject>Image processing</subject><subject>Image reconstruction</subject><subject>Laboratories</subject><subject>Lesions</subject><subject>Longitudinal 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Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hasegawa, Eiichi</au><au>Sweigard, Harry</au><au>Husain, Deeba</au><au>Olivares, Ana M</au><au>Chang, Bo</au><au>Smith, Kaylee E</au><au>Birsner, Amy E</au><au>D'Amato, Robert J</au><au>Michaud, Norman A</au><au>Han, Yinan</au><au>Vavvas, Demetrios G</au><au>Miller, Joan W</au><au>Haider, Neena B</au><au>Connor, Kip M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Characterization of a spontaneous retinal neovascular mouse model</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2014-09-04</date><risdate>2014</risdate><volume>9</volume><issue>9</issue><spage>e106507</spage><epage>e106507</epage><pages>e106507-e106507</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.
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.
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.
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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>25188381</pmid><doi>10.1371/journal.pone.0106507</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1560106967 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Angiogenesis Angiography Animals Biology and Life Sciences Blindness Blood vessels Chemical properties Confocal microscopy Diabetic retinopathy Disease Disease Models, Animal Edema Enzyme-Linked Immunosorbent Assay Epithelium Fluorescein Fluorescein Angiography Image analysis Image processing Image reconstruction Laboratories Lesions Longitudinal Studies Macular degeneration Medical schools Medicine and Health Sciences Mice Microscopic analysis Microscopy Optical Coherence Tomography Photography Photoreceptors Physicians Pigment Epithelium of Eye - pathology Research and Analysis Methods Retina Retina - pathology Retinal Neovascularization - pathology Retinal pigment epithelium Three dimensional analysis Tomography, Optical Coherence Vascular diseases Vascular endothelial growth factor Vascularization Vision |
| title | Characterization of a spontaneous retinal neovascular mouse model |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T21%3A53%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Characterization%20of%20a%20spontaneous%20retinal%20neovascular%20mouse%20model&rft.jtitle=PloS%20one&rft.au=Hasegawa,%20Eiichi&rft.date=2014-09-04&rft.volume=9&rft.issue=9&rft.spage=e106507&rft.epage=e106507&rft.pages=e106507-e106507&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0106507&rft_dat=%3Cgale_plos_%3EA416975692%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1560106967&rft_id=info:pmid/25188381&rft_galeid=A416975692&rft_doaj_id=oai_doaj_org_article_b379734df4a1492daa5105180e04344e&rfr_iscdi=true |