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M. Lawrence, R. Goody, M. Struharik, A. Shafiee, S. P. Bartels, F. J. Lopez; Optimization of Laser-Induced Choroidal Neovascularization in the African Green Monkey. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6156.
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Choroidal neovascularization (CNV) is a primary cause of vision loss in patients with age-related macular degeneration. Laser-induced Bruch’s membrane disruption triggers CNV formation in animal models. We evaluated laser power parameters and endpoint measures to optimize methods for CNV formation and quantification to facilitate drug screening in African green monkeys (AGM).
Adult AGM received 6 laser spots at powers of 350, 550, 750 or 950mW. Spots were 50m diameter, 100ms duration and positioned bilaterally 1.5 disc diameters from the fovea of each eye within the macula. Fluorescein angiography was performed on days 7, 14, 21, 28 and 35 post-laser and masked scoring performed on 21-35 day angiograms. Lesions with bright hyperfluorescence early or mid-transit and late leakage beyond borders of the treated area were considered grade IV. Lesions were also quantified densitometrically. Retina and choroid were flat mounted after necropsy at day 37 and labeled with anti-von Willebrand factor (vWF) antibody and FITC-conjugated secondary antibody.
CNV formation, demonstrated by increased anti-vWF labeling in and around laser spots, was observed in grade III and grade IV lesions. We found no significant changes in incidence of grade IV lesions after day 28 and focused analysis on this time point. Grade III lesions were observed at all laser powers explored with highest incidence at 750 (73%) and 950mW (69%). Grade IV lesions were only observed at 550mW and above, with highest incidence in 950mW lesions (19%), compared to 750 (4%) and 550mW (3%). Incidence of CNV, as demonstrated by grade III or grade IV assignment, was significantly higher in 750 (P=0.0022; P=0.0004) and 950mW (P<0.0001; P<0.0001) laser spots compared respectively to lesions induced by 350 or 550mW laser power. Densitometric analyses corroborated visual scoring.
Based on the demonstration of CNV formation in lesions graded III or IV and highest combined incidence of such lesions, 950mW laser power and scoring of 28 day angiograms has been selected as optimal parameters for screening of therapeutics in the AGM model.
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