Poster Sessions

PREV-3

Juan Amaral

J. Amaral, S. Samtani, M. Campos, R. N. Fariss, S. P. Becerra

Oral Doxycycline Effects on Laser-induced Experimental Choroidal Neovascularization

Severe visual loss due to choroidal neovascularization (CNV) complicates age-related macular degeneration and other retinal diseases. FDA approved treatments for CNV are partially effective. Doxycycline is an antibiotic and a non-specific inhibitor of matrix metalloproteinases, which are important players in neovascular development processes. Laser energy was used to induce CNV in rats. To investigate if doxycycline affects neovessel growth, oral doxycycline was administered to rats for fourteen days starting seven days before laser. A second set of animals received doxycycline for ten days beginning treatment five days after laser. Flat-mount choroid /RPE labeled for nuclei (DAPI), actin cytoskeleton (Phalloidin) and endothelial cells (Isolectin-Ib4) were imaged using confocal microscopy. Z-series were obtained, 3-D reconstructions were generated and neovessel volumes were calculated. Gelatinolytic activity in eye cross-sections was detected by in-situ DQ-gelatin zymography. Doxycyclin treatments inhibited CNV growth by 70% and 22% with 500 and 5 mg/Kg/day, respectively when compared to no-treated controls. Similar doses reverted CNV complexes by 33 % and 53%, respectively. Gelatinolitic activity in the injured area had its peak 5 to 7 days post laser. These results demonstrate that doxycycline effectively inhibited CNV and suggest that doxycyclin could be an important addition in the treatment of this condition.