Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats.

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Gene delivery of calreticulin anti-angiogenic domain attenuates the development of choroidal neovascularization in rats.

Hum Gene Ther. 2017 Mar 31;:

Authors: Bee YS, Tu L, Sheu SJ, Lin HC, Tang JH, Wang JH, Prea SM, Dusting GJ, Wu DC, Zhong J, Bui BV, Tai MH, Liu GS

Abstract
Choroidal neovascularization (CNV) is a common pathological feature in neovascular age-related macular degeneration which is the leading cause of vision loss amongst elderly populations in developed countries. In this study, we evaluated the effect of a novel endogenous inhibitor of angiogenesis, calreticulin anti-angiogenic domain (CAD), subconjunctivally delivered by an adenoviral vector (Ad-CAD) in a rat model of laser-induced CNV. CAD was expressed in Ad-CAD infected cells and inhibited the angiogenic activity in human umbilical vein endothelial cells in vitro. CAD expression was also found in various ocular tissues after in vivo subconjunctival Ad-CAD injection. Via bioluminescence imaging we show that a single subconjunctival injection of Ad-Luci induced the expression of the transgene in the injected eyes within 24 hours, which lasted for at least 112 days. Forty-two days after subconjunctival Ad-CAD retinal structure and function were unaffected, as measured using optical coherence tomography and electroretinography, respectively. After laser injury, subconjunctival Ad-CAD gene delivery significantly inhibited CNV lesions as measured via choroid flat-mounts (51% reduction at 21 days, p<0.001) as well as by fundus fluorescein angiography (19.3%, 28.2%, 31% and 27.5% reductions at day 21, 28, 35 and 42, p<0.05) in rats. Our data suggests that subconjunctival Ad-CAD gene therapy could effectively inhibit laser-induced CNV and might be an attractive therapeutic approach for the management of choroidal neovascularization.

PMID: 28363247 [PubMed - as supplied by publisher]

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