Simultaneous sustained release of VEGF and bFGF from a non-biodegradable implant in the supra-choroidal space induces experimental choroidal neovascularization in both New Zealand white and Dutch belt rabbits.

摘要

Purpose: Previous studies have shown that intravitreal placement of a VEGF/bFGF slow-release implant produces florid robust retinal neovascularization in the Dutch belt rabbit but not in the New Zealand white rabbit. The purpose of this study is to define whether a difference exists in the response between New Zealand white rabbit and Dutch belt rabbit following suprachoroidal implantation of a VEGF/bFGF slow-release pellet for induction of experimental choroidal neovascularization. Methods: Adult New Zealand white (NZW) rabbits (N = 12) and pigmented Dutch belts (N = 6) were implanted transclerally with a non-biodegradable polymeric implant containing both VEGF and bFGF. Negative controls of NZW (N =6) and Dutch belt rabbits (N = 6) were given blank implants. Experimental CNV was assessed over a four-week time period. Eyes were examined by indirect ophthalmoscopy after surgery at 24 hrs, 48 hrs, 4 days, 7 days, and 28 days. Both color fundus and fluorescein angiography (FA) images were captured by a TOPCON 50EX digital IMAGE net retinal camera system at 1, 2, 3, and 4 weeks. CNV was graded between 0 to 3. P values were calculated by using either the Kruskal-Wallis non-parametric test or the Fishera??s exact test at the 4 time points. Results: In all eyes implanted with VEGF/bFGF pellets (N = 18), experimental CNV was observed within 1 week after pellet implantation and continued through weeks 2, 3, and 4. The progression of experimental CNV was similar in both NZW and Dutch belt rabbits. P values were calculated by using either the Kruskal-Wallis non-parametric test or the Fishera??s exact test at the 4 time points. Conclusions: These results demonstrate that experimental CNV is induced rapidly in both types of animals by simultaneous sustained release of VEGF and bFGF in a polymeric implant within the supra-choroidal space. Pigmentation does not appear to change experimental CNV in the rabbit. Progression of experimental rabbit CNV provides a novel pre-clinical tool for rational quantitative structure-activity relationship (QSAR) in retinal drug development, sustained-release drug formulations, and drug delivery device systems in amelioration of exudative AMD.