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Y. Mizutani, C. Tapia, C. Murat, M. J. McLaren, G. Inana; Expression Profiling of Genes Affected in Age-Related Macular Degeneration and Tobacco Smoke-Exposed Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):6133.
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Tobacco smoke has been associated with many health-related problems, including lung diseases, cardiovascular problems, and cancer. Diseases related to the eye are no exception, and age-related macular degeneration (AMD) has been firmly associated with smoking. AMD is a disease thought to be caused by multiple gene defects and environmental factors. Smoking, as a chief environmental factor, most likely affects these genes and may be a clue to uncovering important AMD genes. We have previously identified a number of candidate AMD genes by a custom gene expression profiling strategy called CHANGE. In this study, we used gene expression profiling of second-hand smoke (SHS)-exposed mice to identify genes affected by smoking for comparison with the candidate AMD genes to identify those that fulfill both criteria, making them excellent candidates for AMD.
Groups of ten adult C57BL6 mice were exposed to SHS (TSP = 3-5 mg/m3, 6 hr/day, 5 days/wk) for 3 and 6 weeks in a Teague TE10 smoking machine. RNA was prepared from the retina and retinal pigment epithelium (RPE)/choroid and used for global gene expression profiling using the 38.5K Mouse Exonic Evidence Based Oligonucleotide microarray. The results were subjected to comparative analyses.
The result of the global gene expression profiling demonstrated 2248 and 1089 genes showing differential expression in the 3 and 6 weeks SHS-exposed retina compared to control, respectively, and 4391 and 3529 genes showing differential expression in the 3 and 6 weeks SHS-exposed RPE/choroid compared to control. Pathways shown to be significantly affected by smoke exposure by the GENMAPP and GSAT pathway analyses included the Structural Constituents of the Eye Lens and the Electron Transport Chain. Some of the genes involved in these pathways were also identified as candidate AMD genes in our previous CHANGE analysis.
The comparative analysis of the genes affected by smoking and AMD, identified by the two expression profiling strategies, should be a powerful approach to uncover genes that are important for the mechanism of AMD.
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