July 2019
Volume 60, Issue 9
Free
ARVO Annual Meeting Abstract  |   July 2019
Systemic Delivery Of Endothelial Colony Forming Cells Enables Vascular Integration Into Diabetic Mouse retinas, But Not Diabetic Mouse Retinas Treated With AAV2.COMP-Ang1
Author Affiliations & Notes
  • Lara Carroll
    Department of Opthalmology, Moran Eye Center, Salt Lake City, Utah, United States
  • Xiaohui Zhang
    Department of Opthalmology, Moran Eye Center, Salt Lake City, Utah, United States
  • Yufeng Huang
    School of Medicine, University of Utah, Salt Lake City, Utah, United States
  • Yuanyuan Wu
    Department of Opthalmology, Moran Eye Center, Salt Lake City, Utah, United States
  • Alan W Stitt
    Centre for Experimental Medicine, Queens University Belfast, Belfast, Northern Ireland, Ireland
  • Tim M Curtis
    Centre for Experimental Medicine, Queens University Belfast, Belfast, Northern Ireland, Ireland
  • Reinhold J. Medina
    Centre for Experimental Medicine, Queens University Belfast, Belfast, Northern Ireland, Ireland
  • Balamurali K Ambati
    Department of Opthalmology, Moran Eye Center, Salt Lake City, Utah, United States
  • Footnotes
    Commercial Relationships   Lara Carroll, None; Xiaohui Zhang, None; Yufeng Huang, None; Yuanyuan Wu, None; Alan Stitt, None; Tim Curtis, None; Reinhold Medina, None; Balamurali Ambati, None
  • Footnotes
    Support  NIH Grant 5R01EY026029
Investigative Ophthalmology & Visual Science July 2019, Vol.60, 2724. doi:
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      Lara Carroll, Xiaohui Zhang, Yufeng Huang, Yuanyuan Wu, Alan W Stitt, Tim M Curtis, Reinhold J. Medina, Balamurali K Ambati; Systemic Delivery Of Endothelial Colony Forming Cells Enables Vascular Integration Into Diabetic Mouse retinas, But Not Diabetic Mouse Retinas Treated With AAV2.COMP-Ang1. Invest. Ophthalmol. Vis. Sci. 2019;60(9):2724.

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

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Abstract

Purpose : Endothelial Colony Forming Cells (ECFCs) offer a potential progenitor therapy for repairing vascular beds damaged by diabetes and other neurovascular retinal disorders. Intra-carotid delivery of ECFCs was previously shown to be effective for normalizing vasculature in an oxygen induced retinopathy (OIR) model1. Here we compare outcomes of intravitreal versus intra-carotid artery delivery of ECFCs in retinas of adult diabetic mice. We further tested whether adenoviral associated virus delivery of COMP-Ang1 (a potent, bioengineered version of Angiopoietin 1) would enhance ECFC integration within the diabetic retina.

Methods : AAV2.COMP-Ang1 or AAV2.LacZ was bilaterally injected intravitreally into four-month old Ins2Akita mice. 100 μl of PBS solution containing 100,000 ECFCs (derived from human cord blood) labeled with Q-dot 655 was systemically delivered via the right carotid artery and assayed after 24 or 72 hours. Alternately, 2 μl containing 2,000 ECFCs were injected directly into the vitreous.

Results : Intravitreal injection of ECFCs resulted in uncontrolled endothelial tube assembly primarily within the vitreous of AAV2.COMP-Ang1 treated eyes. In contrast, intra-carotid artery-injected ECFCs explicitly integrated within retinal vessels, but only in the ipsilateral retina (relative to intracarotid injection) of AAV2.LacZ treated mice (2 out of 3 injected mice). Neither the contralateral retina of AAV2.LacZ treated mice (0 out of 3 injected mice), nor the retinas of AAV2.COMP-Ang1 treated mice (0 out of 4 and injected mice) showed any evidence of ECFC integration within retinal vessels.

Conclusions : Intra-carotid delivery of ECFCs into the adult diabetic eye facilitates their direct integration into existing vessels. As labeled ECFCs were not seen after intracarotid injection in AAV2.COMP-Ang1 treated retinas, this suggests that endogenous Ang1/Tie2 pathway activation prevents recruitment and integration of endothelial precursors, which may be of value for treatment of proliferative retinopathies.

1. Reid et al., Stem Cells Transl Med. 2018 Jan;7(1):59-67

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.

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