Laser Induced Choroidal Neovascularization in a Mouse Model of Dry Age–related Macular Degeneration

Abstract

Abstract: : Purpose: A mouse model, transgenic for a mutant cathepsin D (CatDM1), shows changes similar to dry age–related macular degeneration (AMD). To investigate the potential role of accelerated debris accumulation in the pathogenesis of choroidal neovascularization (CNV), we compared the development of laser induced CNV in old CatDM1 and control C57Bl/6J mice. Methods:Lesions were created using a clinical krypton red laser (100µm, 150mW and 0.05s). A small subretinal bubble indicated a break in Bruch’s membrane. Sixteen eyes of 18 month old CatDM1, 10 eyes of 4 month old CatDM1 and 8 eyes of 18 month C57Bl/6J mice were treated, averaging 6 lesions per eye. Color fundus photography and fluorescein angiography were performed after 3 weeks. Hyperfluorescence of lesions was graded from 0 to 4. The eyes were processed for histological correlation. Results: 47% of lesions in older CatDM1 mice were graded as 3 or 4. This was significantly higher than young CatDM1 mice (16%, p<0.001) but similar to age matched C57Bl/6J mice (50%, p=0.77). There was a difference in the rate of coalescence of lesions into larger neovascular complexes, occurring in 54% of older CatDM1 mice and 77% of controls (p=0.009) suggesting a rapid initial growth of CNV in the C57Bl/6J control mice. Conclusions: We observed a difference in the pattern but not in the rate of laser induced CNV formation between CatDM1 and control mice. Gene array analysis has shown changes in UV–protection, anti–apoptotic, anti–inflammatory, antiproliferative and angiostatic gene expression in the CatD1 mice. These changes might be responsible for the lack of increased CNV formation in the CatDM1 mice despite of the presence of basal laminar and linear deposits in the Bruch’s membrane. Alternatively, these results support a separation of the mechanisms responsible for dry and wet AMD formation.

Keywords: age–related macular degeneration • laser • choroid: neovascularization