Enhanced Delivery of Mitomycin C–Dextran Conjugates with Transpupillary Thermotherapy for Experimental Choroidal Neovascularization

Abstract

Abstract: : Purpose: We have shown that transpupillary thermotherapy (TTT) could increase an accumulation of 70kd macromolecules around choroidal neovascularization (CNV) in rats for 12 hours temporarily (2004 ARVO poster.) In the present study, we investigated a novel strategy for the treatment of CNV, which consisted of administration of 70kd macromollecullar drug following TTT. Methods:A modified slit lamp, which was installed with two laser wavelenghs (490 nm for illumination and fluorescein excitation and 810 nm for hyperthermia), was developed for TTT. Following TTT (4 minutes) on rat CNV with the modified slit lamp, Mitomycin C–Dextran conjugates (MW 70kd, including 0.7mg MMC) was administered intravenously. Two weeks after the treatment, fluorescein angiography was performed to detect the area of CNV and the images were computerized to evaluate fluorescein intensity. Fluorescein leakage was scored on a four–grade scale. The animals were sacrificed and the CNV lesions were evaluated histologically. All results were compared to those of eyes with single administration of TTT, MMC, or MMC–Dextran. Results:Concomitant administration of MMC–Dextran conjugates and TTT inhibited the development of CNV in rats with an average score of 0.83±0.31 (mean ± SEM), though single administration of TTT (2.38±0.45), MMC (1.80±0.22), or MMC–Dextran (1.83±0.17) did not (p<0.001). Conclusions:Our results showed that combination therapy of MMC–Dextran and TTT significantly inhibited the development of rat CNV. The present method had potential that we could treat CNV safely and effectively with a low dose of MMC.

Keywords: age–related macular degeneration • laser • drug toxicity/drug effects