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D. Rabin, T. C. Bruice, T. T. You, C. G. Wong; Both Edema and Leakage Are Expressed and Are Separable in Long-Term Experimental CNV via Sustained Simultaneous Release of VEGF and bFGF Within the Suprachoroidal Space Through Transcleral Implantation of a Delivery Device. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1374.
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The goal of this study is to determine if the pathologic components of edema and leakage that are both present in florid experimental CNV induced through simultaneous long-term suprachoroidal release of VEGF and bFGF can be separated through changes to the cross-linkage levels of the non-biodegradable delivery device.
Adult female New Zealand white rabbits (N=10) were implanted transclerally in the artificially created suprachoroidal space (Wong et al., 2001 Curr Eye Res) with either a high cross-linkage (N = 5) or a low cross-linkage (N = 5) non-biodegradable VEGF/bFGF-containing delivery device. A negative control (N = 1) was implanted with a blank delivery device without growth factors. Both bFGF and VEGF release from the polymeric devices were monitored in vitro by ELISA. Animals were examined weekly by indirect ophthalmolscopy over the four-week study period. A TOPCON 50EX digital IMAGE Net retinal camera system was utilized to capture the color fundus and fluorescein angiograms on a weekly basis.
In the group with the low cross-linkage polymeric device that contained both VEGF and bFGF, edema appeared rapidly between Day 7 and Day 14 and was followed by fluorescein leakage by Day 14 that was stable over the course of the study. In the second group with the high cross-linkage delivery device, though leakage appeared between Day 14 and Day 21 and was maintained over the study period, edema did not occur.
Long-term stability of lesions, separation of edema from leakage, and reproducibility of the suprachoroidal VEGF/bFGF rabbit CNV model in this preliminary study suggest new practical approaches for rational QSAR therapeutic development of novel drugs, formulations, and delivery devices for amelioration and ultimate prevention of WMD.
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