September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Progressive experimental choroidal neovascularization of both New Zealand White and Dutch belt rabbit after sustained release of both VEGF and bFGF within the subchoroidal space
Author Affiliations & Notes
  • Corinne G Wong
    Ophthalmology & Vision Sciences, SCLERA LLC, Carlsbad, California, United States
  • Fred N. Ross-Cisneros
    Ophthalmology, UCLA School of Medicine, Los Angeles, California, United States
  • Thomas C Bruice
    UCLA School of Medicine, Los Angeles, California, United States
  • Grit Zahn
    Consulting, Berlin, Germany
  • Tim You
    Orange County Retina Group, Santa Ana, California, United States
  • Footnotes
    Commercial Relationships   Corinne Wong, None; Fred Ross-Cisneros, None; Thomas Bruice, None; Grit Zahn, None; Tim You, None
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Corinne G Wong, Fred N. Ross-Cisneros, Thomas C Bruice, Grit Zahn, Tim You; Progressive experimental choroidal neovascularization of both New Zealand White and Dutch belt rabbit after sustained release of both VEGF and bFGF within the subchoroidal space. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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

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Abstract

Purpose : This study is to determine whether sustained release of both VEGF and bFGF from a non-biodegradable implant that is placed trans-sclerally within the subchoroidal space in both New Zealand white (NZW) and pigmented Dutch belt rabbits produces efficient progressive choroidal neovascularization (CNV).

Methods : Non-biodegradable Hydron pellets containing both VEGF and bFGF were implanted trans-sclerally within the subchoroidal space of adult pigmented Dutch belt rabbits (N = 6) and NZW rabbits (N = 8). As negative controls, both Dutch belt rabbits (N = 6) and NZW rabbits (N = 4) were implanted trans-sclerally with blank implants that contained no growth factors. N = 24 rabbits were utilized in this study. Experimental CNV was assessed weekly over a four-week time period with ophthalmic exams, color fundus photography, and fluorescein angiography (FA). Both general histology and immunohistochemistry (IHC) were performed at the end of the four-week period.

Results : In both the two groups that received subchoroidal implants containing VEGF and bFGF, strong fluorescein leakage is observed at weeks 2,3, and 4 (p<0.005) with no initial leakage seen in week 1. The two negative control groups with implants containing no growth factors demonstrated no flourescein leakage at any time points throughout the four-week study period. Both histology and IHC confirmed that experimental CNV with new subretinal blood vessel growth occurred in eyes with subchoroidal VEGF/bFGF implants as compared in eyes with blank implants. RPE thickening can be seen in this rabbit model along with melanin granules of the RPE being transferred from the basal to apical side.

Conclusions : Earlier studies indicate the efficient utility of these growth factor-containing implants to induce robust and efficient experimental retinal NV in the rabbit eye reproducibly through intravitreal implantation. This study demonstrates that trans-scleral implantation within the subchoroidal space of a non-biodegradable device containing both VEGF and bFGF is a viable approach in producing efficient, robust, and reproducible experimental rabbit CNV for evaluation of potential therapeutics against advanced neovascular AMD and in defining mechanisms of abnormal subretinal blood vessel growth from the choroid to the RPE that lead to advanced AMD.

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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