Abstract
Abstract: :
Purpose: Previously we have reported a great diversity of angiogenic potential between different inbred strains of mice. In this study we investigate the influence of genetic background on CNV. Methods: We have utilized the murine laser induced CNV model in C57BL/6J, DBA/2J, 11 recombinant inbred (BXD–RI) strains derived from C57BL/6J and DBA/2J (with the same steel grey coat), and 129S1/SvImJ mice. The CNV size was measured 2 weeks after the laser treatment by FITC–dextran angiography, choroidal flatmount, and histological examination. Results: The mean hyperfluorescent area in FITC–dextran angiography was correlated with the mean CNV area in choroidal flatmount of all treated strains. Although the choroidal pigment of 129S1/SvImJ was lighter than C57BL/6J (thus absorbing less laser energy), the CNV size of 129S1/SvImJ was significant larger than C57BL/6J (p<0.01). Individual recombinant strains demonstrated large differences in CNV, which ranged from lower than either of the parental strains (BXD–18) to higher than either of the parental strains (BXD–16, 33 and 39). The range of phenotypic responses was over 2 fold. Conclusions: The combination of FITC–dextran angiography, choroidal flatmount and histological examination is a powerful tool for analysis of laser–induced CNV. In this study, we have demonstrated that genetic modifiers are major contributors to CNV. Genetic mapping of phenotypes from the laser induced CNV model is ongoing. Future studies may dissect the role of unique genetic changes that influence ones susceptibility to CNV, as well as predict the severity of outcome.
Keywords: age–related macular degeneration • choroid: neovascularization • laser