June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Gene delivery of vasostatin via a self-complementary adeno-associated virus 2 inhibits retinal neovascularization in a rat model of oxygen-induced retinopathy
Author Affiliations & Notes
  • Leilei Tu
    Department of ophthalmology, the First Affiliated Hospital of Jinan University, Guangzhou, China
    Centre for eye research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
  • Jiang-Hui Wang
    Centre for eye research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery , University of Melbourne, Melbourne, Victoria, Australia
  • Ming-Hong Tai
    Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
  • Gregory Dusting
    Centre for eye research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery , University of Melbourne, Melbourne, Victoria, Australia
  • Guei-Sheung Liu
    Centre for eye research Australia, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia
    Ophthalmology, Department of Surgery , University of Melbourne, Melbourne, Victoria, Australia
  • Footnotes
    Commercial Relationships   Leilei Tu, None; Jiang-Hui Wang, None; Ming-Hong Tai, None; Gregory Dusting, None; Guei-Sheung Liu, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3443. doi:
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      Leilei Tu, Jiang-Hui Wang, Ming-Hong Tai, Gregory Dusting, Guei-Sheung Liu; Gene delivery of vasostatin via a self-complementary adeno-associated virus 2 inhibits retinal neovascularization in a rat model of oxygen-induced retinopathy
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):3443.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Retinal neovascularization is a common pathological feature in diabetic retinopathy and retinopathy of prematurity, leading to severe vision damage or irreversible blindness. We evaluated the efficacy of a novel endogenous inhibitor of angiogenesis, vasostatin (VS180) and its functional fragment of 112 residues, vasostatin-like peptide 112 (VS112) via a self-complementary adeno-associated virus 2 (scAAV2)-mediated intravitreal gene delivery in an experimental rat model of oxygen-induced retinopathy (OIR).

Methods : Anti-angiogenic effects of VS112 and VS180 delivered via a scAAV2 vector in vitro were validated by the migration and tube formation on Matrigel of human umbilical vein endothelial cells (HUVECs). Retinal neovascularization was induced by exposing newborn rats to 80% oxygen for 21 hours and returned to room air for 3 hours every day during the first 14 days of life, and then returning them to room air for another 4 days. ScAAV2-mCherry, scAAV2-VS112 or scAAV2-VS180 were injected intravitreally at postnatal day 7 (P7) and the eyes were harvested on day 18 (P18) for the quantification of retinal vaso-obliteration and neovascularization, respectively.

Results : The expression of VS112 or VS180 was elevated in cells infected with scAAV-VS112 or scAAV2-VS180 respectively, and both inhibited the angiogenic activity in HUVECs in vitro. Intravitreal scAAV2-mediated gene delivery was able to effectively transduce a reporter gene (mCherry) in the rat retina within 10 days. ScAAV2-VS112 or scAAV2-VS180 gene delivery significantly inhibited the retinal neovascularization (VS112: 1.29 ± 0.08%, VS180: 1.38 ± 0.11%) compared to those that received scAAV2-mCherry (2.62 ± 0.18%, P<0.001). Unexpectedly, there was a significant increase in retinal vaso-obliteration in eyes that had received scAAV2-VS112 (39.7 ± 4.3%) compared to those injected with scAAV2-mCherry (19.9 ± 4.3%) or scAAV2-VS180 (22.3 ± 4.3%).

Conclusions : Intravitreal scAAV2-VS112 and scAAV2-VS180 gene therapy effectively inhibit retinal neovascularization in a rat model of OIR, but VS112 might also influence blood vessel development. Thus, scAAV2-VS180 gene therapy has potential as a therapeutic approach for retinal neovascularization.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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