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N. M. Buchanan, C. E. Bigelow, S. H. Poor, J. Demirs, G. S. Bounoutas, I. L. Jones, B. Jaffee, M. E. McLaughlin; Pseudo-AMD Changes in Wild-Type C57Bl/6 Mice. Invest. Ophthalmol. Vis. Sci. 2009;50(13):779.
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One of the major challenges in developing new therapies for the treatment of dry AMD is the lack of an accurate, reproducible mouse model in which compounds can be tested. While several publications report AMD-like changes in various genetically engineered mice, a rigorous study of wild-type mice to define the range of normal ocular pathology is lacking.
To date, 10 male and 15 female C57Bl/6 mice have been aged for up to 10 months. In addition, 8 male and 8 female C57Bl/6 mice have been maintained on a high fat diet with the oxidant hydroquinone for up to 10 months. Mice have been examined by indirect ophthalmoscopy (IO), optical coherence tomography (OCT), and electroretinography (ERG). Samples for histology were collected at 2, 4 and 10 months, and samples for electron microscopy were collected for 10 months.
Three lesions mimicking changes seen in AMD have been identified. 1) By IO small (40-50 microns), ill-defined, whitish yellow, drusen-like deposits were seen in approximately 81% of C57Bl/6 mice. The number of deposits was increased in mice fed the high fat plus hydroquinone diet. The histologic correlate of these lesions is still under investigation. 2) Also by IO, approximately 9% of mice had focal, central retinochoroidal atrophy, that was first recognized at the 3 month examination. 3) By histology, PAS-positive, sub-RPE deposits (5-30 microns in diameter) were identified at the ora serrata. These lesions were not visualized by IO or OCT due to their peripheral location.
Pseudo-AMD changes mimicking drusen and geographic atrophy are present in wild-type C57Bl/6 mice. An awareness of these changes is critical in order to determine whether or not individual gene mutations cause an AMD-like phenotype in mice.
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