April 2009
Volume 50, Issue 13
ARVO Annual Meeting Abstract  |   April 2009
Natural History of Progressive Experimental CNV in the Rabbit After Sustained Release of Both VEGF and bFGF Within the Supra-Choroidal Space
Author Affiliations & Notes
  • C. G. Wong
    Ophthalmic Drug Dev, SCLERA LLC, Carlsbad, California
  • T. You
    Orange County Medical Group, Irvine, California
  • R. Carvalho
    Targeted Therapeutic Technologies, Irvine, California
  • Footnotes
    Commercial Relationships  C.G. Wong, None; T. You, None; R. Carvalho, None.
  • Footnotes
    Support  None.
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 2970. doi:
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      C. G. Wong, T. You, R. Carvalho; Natural History of Progressive Experimental CNV in the Rabbit After Sustained Release of Both VEGF and bFGF Within the Supra-Choroidal Space. Invest. Ophthalmol. Vis. Sci. 2009;50(13):2970.

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

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Purpose: : The goal of this study to define clinicopathologic correlation and investigate mechanisms in rabbit of reproducible and progressive experimental CNV, which is induced by suprachoroidal release of both VEGF and bFGF without mechanical damage in either Bruch’s membrane or the overlying retina.

Methods: : A sustained-release device for both VEGF and bFGF has been shown to produce florid irreversible retinal NV in the rabbit after intravitreal implantation (Wong et al., 2001) and to produce highly reproducible CNV following transcleral implantation within the suprachoroidal space of a Hydron implant containing both VEGF and bFGF (Carvalho et al, 2001) over a short time period. Adult female New Zealand white rabbits (N=6) were induced with experimental CNV, which developed within 2 wks in 85% of the animals; indirect ophthalmic exams were performed on a weekly basis for 6 wks. A TOPCON 50EX digital IMAGE Net retinal camera system was utilized to capture color fundus & fluorescein angiograms. Correlation of light microscopic studies with fluorescein angiography was performed.

Results: : Experimental CNV penetrated Bruch’s membrane with phagocytosis of the red blood cells (RBCs) by the RPE from the basal side. Melanin granules of the RPE cells were transferred from the basal to apical side. Most RPE cells became distended from engulfing so many RBCs. Small spherical pieces of RBCs which were phagocytosed by the RPE cells appear to be located within the cytoplasm of the RPE cells. Lesions that demonstrated both leaking and pooling of fluorescein contained subretinal vessels.

Conclusions: : Effectiveness, ease, long-term stability of lesions, and high reproducibility of the suprachoroidal VEGF/bFGF rabbit CNV model within a short time frame suggest new practical approaches for defining novel low-cost compounds in the amelioration of AMD. The relevance of this rabbit CNV model has been shown by its similar profiles of efficacy for inhibiting CNV formation by experimental drugs with laser-induced CNV in monkey. Parallel studies of this experimental CNV model in both the rabbit and monkey along with potential extension of the CNV for up 6 months will support additional rational QSAR development of novel drugs, formulations, and delivery devices for the amelioration and ultimate prevention of both dry and wet AMD.

Keywords: choroid: neovascularization • choroid • growth factors/growth factor receptors 

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