Abstract
Purpose: :
The goal of this study is to define whether long-term experimental rabbit choroidal neovascularization (CNV), which is induced by sustained release of both VEGF and bFGF in the suprachoroidal space, can be utilized in defining potential synergistic interactions of Lucentis (ranibizumab) with other small molecules for rational QSAR development of more effective low-cost therapeutic approaches in ameliorating wet AMD (WMD).
Methods: :
Adult female New Zealand white rabbits (N=6) was induced with experimental CNV by sustained simultanenous release of VEGF and bFGF within the suprachoroidal space after transcleral implant of a non-biodegradable device (Wong et al., 2001 Curr Eye Res). Experimental CNV was allowed to develop for either 2 weeks (N = 2) or 4 weeks (N = 2) prior to intravitreal (IVT) injection of 50 ug Lucentis while a control group (N = 2) received IVT 50 ul phosphate-buffered saline (PBS). Indirect ophthalmic exams were performed on a weekly basis for 10 weeks. A TOPCON 50EX digital IMAGE Net retinal camera system was utilized to capture the color fundus & fluorescein angiograms. Severity of lesions was graded on a scale of 0, +1, +2, +3, & +4.
Results: :
Experimental CNV lesions developed reproducibly in all animals prior to IVT injections of either Lucentis or PBS. Lesions in the control non-Lucentis group showed no signs of regression during the 10-week study period. A single IVT injection of Lucentis at 2 weeks after induction of CNV reversed the lesions during the subsequent 8 week observation period. Also, a single IVT dose of Lucentis at 4 weeks after induction of CNV in both animals stopped leakage within a week, which was maintained through the remaining 6 weeks study period in 1 animal. The other animal presented at 14 days later with robust leakage, which continued through the remainder of the study.
Conclusions: :
Effectiveness, ease, long-term stability of lesions, and reproducibility of the suprachoroidal VEGF/bFGF rabbit CNV model in this preliminary study suggest new practical approaches for defining potential synergistic actions of Lucentis with other potentially low-cost compounds. Further studies of this experimental CNV model in both the rabbit and non-human primate along with extension of the CNV for up 6 months will support additional rational QSAR development of novel drugs, formulations, and delivery devices for amelioration and ultimate prevention of WMD.
Keywords: age-related macular degeneration • choroid: neovascularization • retina