September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Systemic Distribution of AAV10.COMPAng1 in the Ins2Akita mouse
Author Affiliations & Notes
  • Malkit Kaur Singh
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Hironori Uehara
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Xiaohui Zhang
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Deepti Vashist
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Lara Carroll
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Bonnie Archer
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Yufeng Huang
    Nephrology, University of Utah, Salt Lake City, Utah, United States
  • Balamurali Ambati
    John A. Moran Eye Center, University of Utah, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Malkit Singh, None; Hironori Uehara, None; Xiaohui Zhang, None; Deepti Vashist, None; Lara Carroll, None; Bonnie Archer, None; Yufeng Huang, None; Balamurali Ambati, None
  • Footnotes
    Support  RPB Unrestricted Grant
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 5056. doi:
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      Malkit Kaur Singh, Hironori Uehara, Xiaohui Zhang, Deepti Vashist, Lara Carroll, Bonnie Archer, Yufeng Huang, Balamurali Ambati; Systemic Distribution of AAV10.COMPAng1 in the Ins2Akita mouse. Invest. Ophthalmol. Vis. Sci. 2016;57(12):5056.

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

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Abstract

Purpose : Diabetic retinopathy is the leading cause of new blindness among adults aged 20-74 years. The pathogenesis of diabetic retinopathy involves vascular hyperpermeability and capillary dropout. Angiopoietin 1 acting on the Tie2 receptor is known to be important in vasculature stabilization. Previously, we showed that intravitreal injection of AAV2.COMPAng1 (a more stable analogue of Angiopoietin 1) prevents vascular loss and leakage and preserves the visual acuity in a diabetic mouse model. In this study, we examine the systemic distribution and effect on visual function of AAV10.COMPAng1 after intravenous injection in a diabetic mouse model.

Methods : We treated type 1 diabetic Akita Ins2+/- male mice at 2 months of age with one tail vein injection of an adeno-associated virus expressing COMPAng1 (AAV10.COMPAng1), AAV10.GFP, or phosphate buffered saline as a control. Two weeks post-injection, we harvested lung, liver, kidney, and eye to examine GFP expression. Serum level of COMPAng1 protein were measured by Elisa.

Results : Through tail vein injection, we delivered the 1x1011 each AAV particle. Mice did not show any adverse effects to this treatment. At two weeks, we found the most GFP expression was in lung, followed by the liver. However, we did not find GFP positive cells in mouse eye. Serum COMPAng1 was ~0.5 mcg/mL. Thus, AAV10 did not transduce the gene in the eye but can maintain a high level of COMPAng1 in serum.

Conclusions : Serum Angiopoietin 2, which is an antagonist of Angiopoietin 1, is increased in the patients with diabetic retinopathy and probably inhibits Angiopoietin 1 function. We now demonstrate that although AAV10 does not transduce the gene in the eye after systemic delivery, serum COMPAng1 can be expressed at therapeutic levels by a single AAV10 intravenous injection.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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