June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model
Author Affiliations & Notes
  • Jeffrey Tran
    School of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
  • Caroline Craven
    School of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
  • Kathy Wabner
    School of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
    University of Minnesota , Minneapolis, Minnesota, United States
  • Jenn Schmit
    School of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
    University of Minnesota , Minneapolis, Minnesota, United States
  • Uday B Kompella
    School of Pharmacy, University of Colorado, Aurora, Colorado, United States
  • Hans E Grossniklaus
    School of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
  • Timothy W Olsen
    School of Medicine, Emory University School of Medicine, Atlanta, Georgia, United States
  • Footnotes
    Commercial Relationships   Jeffrey Tran, None; Caroline Craven, None; Kathy Wabner, None; Jenn Schmit, None; Uday Kompella, None; Hans Grossniklaus, None; Timothy Olsen, None
  • Footnotes
    Support  This work was supported by NIH/NEI RO1 EY022097, Georgia Research Alliance, and an unrestricted departmental grant from Research to Prevent Blindness (RPB)
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 250. doi:
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    • Get Citation

      Jeffrey Tran, Caroline Craven, Kathy Wabner, Jenn Schmit, Uday B Kompella, Hans E Grossniklaus, Timothy W Olsen; A Pharmacodynamic Analysis of Choroidal Neovascularization in a Porcine Model. Invest. Ophthalmol. Vis. Sci. 2017;58(8):250.

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

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Abstract

Purpose : Delaying the natural progression of pathologic macular aging to maintain sight for the large numbers of individuals affected by age related macular degeneration (AMD). The goal of this in vivo, pre-clinical study is to optimize pharmacodelivery to enhance macular pharmacotherapies by comparing the efficacy of microneedle delivered suprachoroidal (SC) pazopanib to intravitreal (Ivit) delivery of pazopanib, bevacizumab, or a fusion protein hI-con-1 versus controls on the growth of type 2 choroidal neovascularization (CNV) in the porcine model.

Methods : Forty-one pigs were injected either on the day of CNV induction or post-induction day #14 (hI-con1) with either 2.5 mg Ivit bevacizumab (n=9), 1 mg pazopanib (n=9), 300 Ivit mg hI-con1 (n=4), or 1 mg SC pazopanib (n=9), versus 10 vehicle controls (3 SC + 7 Ivit = 10). Pigs were euthanized at postoperative week 2 (11), 3 (8), 4 (11), and 8 (11). Eyes were enucleated and fixed for histology. The size of the type 2 CNV complex was determined by measuring lesion size from histologic sections. Immunostaining for cytotoxic T-cells was performed on the hI-con1 and control eyes.

Results : In 39 of 41 (95%) eyes, type 2 CNV lesions were identified. One CNV lesion was lost with the retinal tissue during dissection. Another animal was euthanized due to surgical complications. For mean CNV size comparisons, Ivit pazopanib had smaller height measures (90 ± 20 µm) versus controls (180 ± 20 µm; p=0.009), and Ivit pazopanib had smaller maximum CNV height (174 ± 43 µm) compared to SC pazopanib (448 ± 25 µm; p=0.018). The mean lesion size in hI-con-1 treated animals was smaller than controls (p=0.11) although the number of animals was small. Immunostaining did not detect cytotoxic T-cells at the time of enucleation.

Conclusions : Intravitreal pazopanib and hI-con-1 treatments reduced the size of CNV lesions versus controls. The pig model has a near 100% success rate of type 2 CNV induction and is an excellent preclinical model to study and assess CNV growth and therapeutic response.

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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