Age-related macular degeneration (AMD) is the leading cause of irreversible severe central visual loss in the aged population. Various studies suggest that AMD has a significant genetic component. Current evidence supports the hypothesis that gene variation causes predisposition to the disease. We initiated the project in early 2003 by recruiting advanced AMD patients and normal controls. So far over 400 subjects have been enrolled and 53 histopathological cases with AMD were collected. We also received 835 DNA smaples from Blue Mountain Eye Study in Australia and 534 DNA smaples from AREDS. We are comparing the allelic frequencies of single nucleotide polymorphisms (SNPs) within candidate genes between AMD and control subjects followed by the functional study of these SNPs by in vitro and/or in vivo experiments. Through this approach, we identify genetic risk factors of AMD and understand the role of these gene variations in the pathogenesis of the disease. Based on the information obtained from above experiments and recent literature, gene engineered animal are generated to establish the disease model. In FY2006, we have accomplished the following: 1. Completion of 15000 SNPs typing; 2. Report of synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on AMD predisposition; 3. Characterization of the retinal lesion of the CX3CR1/CCL2 double knock-out mice, a murine model of AMD, which we developed; 4. Confirmation of LOC association with AMD; and 5. Confirmation of the involvement of ER protein in the pathogenesis of retinal digeneration. Four articles were published and 9 abstracts wre presented in various meetings including FASEB, ARVO and Global Chinese Ophthalmological Conference in this time period. We are preparing several more manuscripts.

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National Eye Institute (NEI)
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U.S. National Eye Institute
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Popp, Nicholas; Chu, Xi K; Shen, Defen et al. (2013) Evaluating Potential Therapies in a Mouse Model of Focal Retinal Degeneration with Age-related Macular Degeneration (AMD)-Like Lesions. J Clin Exp Ophthalmol 4:1000296
Tuo, Jingsheng; Ross, Robert J; Herzlich, Alexandra A et al. (2009) A high omega-3 fatty acid diet reduces retinal lesions in a murine model of macular degeneration. Am J Pathol 175:799-807
Ross, Robert J; Verma, Varun; Rosenberg, Kevin I et al. (2007) Genetic markers and biomarkers for age-related macular degeneration. Expert Rev Ophthalmol 2:443-457
Tuo, Jingsheng; Bojanowski, Christine M; Zhou, Min et al. (2007) Murine ccl2/cx3cr1 deficiency results in retinal lesions mimicking human age-related macular degeneration. Invest Ophthalmol Vis Sci 48:3827-36
Ross, Robert J; Bojanowski, Christine M; Wang, Jie Jin et al. (2007) The LOC387715 polymorphism and age-related macular degeneration: replication in three case-control samples. Invest Ophthalmol Vis Sci 48:1128-32
Tuo, Jingsheng; Ning, Baitang; Bojanowski, Christine M et al. (2006) Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition. Proc Natl Acad Sci U S A 103:9256-61
Bojanowski, Christine M; Shen, Defen; Chew, Emily Y et al. (2006) An apolipoprotein E variant may protect against age-related macular degeneration through cytokine regulation. Environ Mol Mutagen 47:594-602
Shen, Defen; Wen, Rong; Tuo, Jingsheng et al. (2006) Exacerbation of retinal degeneration and choroidal neovascularization induced by subretinal injection of Matrigel in CCL2/MCP-1-deficient mice. Ophthalmic Res 38:71-3
Chan, C-C; Tuo, J; Bojanowski, C M et al. (2005) Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration. Histol Histopathol 20:857-63
Tuo, Jingsheng; Bojanowski, Christine M; Chan, Chi-Chao (2004) Genetic factors of age-related macular degeneration. Prog Retin Eye Res 23:229-49

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