AAV-mediated gene delivery of the calreticulin anti-angiogenic domain inhibits ocular neovascularization View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2018-02

AUTHORS

Leilei Tu, Jiang-Hui Wang, Veluchamy A. Barathi, Selwyn M. Prea, Zheng He, Jia Hui Lee, James Bender, Anna E. King, Grant J. Logan, Ian E. Alexander, Youn-Shen Bee, Ming-Hong Tai, Gregory J. Dusting, Bang V. Bui, Jingxiang Zhong, Guei-Sheung Liu

ABSTRACT

Ocular neovascularization is a common pathological feature in diabetic retinopathy and neovascular age-related macular degeneration that can lead to severe vision loss. We evaluated the therapeutic efficacy of a novel endogenous inhibitor of angiogenesis, the calreticulin anti-angiogenic domain (CAD180), and its functional 112-residue fragment, CAD-like peptide 112 (CAD112), delivered using a self-complementary adeno-associated virus serotype 2 (scAAV2) in rodent models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. The expression of CAD180 and CAD112 was elevated in human umbilical vein endothelial cells transduced with scAAV2-CAD180 or scAAV2-CAD112, respectively, and both inhibited angiogenic activity in vitro. Intravitreal gene delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly inhibited ischemia-induced retinal neovascularization in rat eyes (CAD180: 52.7% reduction; CAD112: 49.2% reduction) compared to scAAV2-mCherry, as measured in retinal flatmounts stained with isolectin B4. Moreover, the retinal structure and function were unaffected by scAAV2-CAD180 or scAAV2-CAD112, as measured by optical coherence tomography and electroretinography. Moreover, subretinal delivery of scAAV2-CAD180 or scAAV2-CAD112 significantly attenuated laser-induced choroidal neovascularization in mouse eyes compared to scAAV2-mCherry, as measured by fundus fluorescein angiography (CAD180: 62.4% reduction; CAD112: 57.5% reduction) and choroidal flatmounts (CAD180: 40.21% reduction; CAD112: 43.03% reduction). Gene delivery using scAAV2-CAD180 or scAAV2-CAD112 has significant potential as a therapeutic option for the management of ocular neovascularization. More... »

PAGES

95-109

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10456-017-9591-4

DOI

http://dx.doi.org/10.1007/s10456-017-9591-4

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100272416

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29318471


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