May 2004
Volume 45, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2004
Predictive Mechanism–Based Animal Models of Intraocular Neovascular Diseases for Rapid QSAR Drug Target Identification and Validation
Author Affiliations & Notes
  • C. Wong
    Ophthalmology, Univ of California, Irvine, CA
    SCLERA LLC, Newport Beach, CA
  • H.T. Hsu
    Ophthalmology, Univ of California, Irvine, CA
  • Footnotes
    Commercial Relationships  C. Wong, University of California, Irvine P; H.T. Hsu, None.
  • Footnotes
    Support  NIH RO1 Grant EYO 06147/TRDRP
Investigative Ophthalmology & Visual Science May 2004, Vol.45, 460. doi:
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      C. Wong, H.T. Hsu; Predictive Mechanism–Based Animal Models of Intraocular Neovascular Diseases for Rapid QSAR Drug Target Identification and Validation . Invest. Ophthalmol. Vis. Sci. 2004;45(13):460.

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

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Abstract

Abstract: : Purpose: To evaluate if experimental florid non–regressing retinal NV and CNV that are produced in the rabbit by sustained release of VEGF/bFGF from a non–biodegradable matrix are predictive models that will allow for rational structure/function development of therapeutic agents against key angiogenic targets and subsequent validation. Methods: A reproducible non–regressing rabbit model of florid retinal NV simulating proliferative diabetic retinopathy (Wong et al., 2001) is produced by intravitreal implantation of a sustained–release pellet (1.0 to 1.5 mm in diameter) containing both VEGF (15 ug) and bFGF (20 ug) while experimental CNV with an intact retina is induced through transcleral implantation of the VEGF/bFGF pellet (0.75 to 1.00 mm in diameter) within the suprachoroidal space (Carvalho et al., 2000; Ross–Cisneros et al., 2003). Different chemical classes that include both oligonucleotides with high binding capacities for key proteins that are involved in cellular proliferation and proteins that target key pathways downstream from VEGF receptor signaling are administered intravitreally in 50 to 100 ul aliquots at time of implantation, 5, 7, or 14 days later (N = 5 per time points). FAs and fundus photography are obtained at 0, 7, 14, and 28 days later. Subjective grading of neovascularization is between 0 and 4 for both retinal NV and CNV. Results: Retinal detachments are not observed after pellet implantation either intravitreally through the pars plana or transclerally in the suprachoroidal space over the course of the studies. Key observation is that non–VEGF–targeted molecules are effective in the amelioration of intraocular angiogenesis. Conclusion: This preliminary study suggests the ability of these VEGF/bFGF–induced animal models to predict the different chemical classes that can ameliorate intraocular angiogenesis, which occurs in both diabetic retinopathy (DR) and the exudative or wet form of AMD. Hence, pathogenesis–based prophylactic and therapeutic treatments presumably can be designed for the early stages of both DR and wet AMD by utilizing these mechanism–based animal models in addition to other models that are produced by non–specific trauma.

Keywords: age–related macular degeneration • choroid: neovascularization • retinal neovascularization 
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