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C. M. Aderman, K. M. Connor, J. Chen, K. L. Willett, O. P. Aspegren, J. P. SanGiovanni, E. Y. Chew, N. Salem, Jr., L. E. H. Smith; Gene Profiles of Omega-3 and Omega-6 PUFA Fed Mice With Retinopathy. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3447.
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We have previously reported that mice with elevated levels of omega-3 polyunsaturated fatty acids, through either dietary or genetic means, are protected from retinopathy through enhanced vessel regrowth. Mice on a diet enriched in omega-3 fatty acids had decreased levels of microglial-derived TNF-alpha in a model of oxygen induced retinopathy. To further investigate the protective properties of omega-3 fatty acids in pathological neovascularization, we performed Illumina microarray analysis on retinas from mice on diets rich in either omega-3 or omega-6 polyunsaturated fatty acids (PUFAs).
Beginning at postnatal day 0 (P0), mothers were fed diets enriched with either omega-3 or omega-6 PUFAs. To induce vessel loss, and subsequent pathological neovascularization, nursing mothers and pups were exposed to 75% oxygen from P7 to P12 and returned to room air and sacrificed at P17. One eye from each mouse was isolated and lectin-stained for quantification of neovascularization and vaso-obliteration. Contralateral retinas from each group were isolated and flash frozen using RNase-free techniques. Total RNA was extracted and prepared for Illumina microarray analysis using the MouseRef-6 chip. Data was acquired using the Illumina BeadStudio software and further analysis was performed using Significance Analysis of Microarray (SAM), Gene Set Enrichment Analysis (GSEA), and J-Express Pro 2.7 software. A set of differentially expressed genes were validated with real-time PCR.
In line with previous studies, both vaso-obliteration (VO) and neovascularization (NV) were more severe in retinas of omega-6 fed mice (%VO: 19.0 ± 1.0; %NV: 10.2 ± 0.7) than in retinas of their omega-3 fed counterparts (%VO: 14.7 ± 1.5, p < 0.05; %NV: 2.9 ± 0.5, p < 0.001) following oxygen exposure. Contralateral retinas from these mice were used for Illumina microarray analysis, which showed a 2-8 fold upregulation of activated macrophage, inflammation, angiogenesis, and adhesion markers in omega-6 fed mice.
These findings suggest that upregulation of adhesion markers in omega-6 fed mice may be responsible for recruiting inflammatory cells and activated macrophages in the retina, resulting in an increased production of pro-angiogenic signals and more severe pathological neovascularization.
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