Age-related macular degeneration (AMD) is the leading cause of irreversible central visual loss in the aged population in the world. Various studies suggest that AMD has a significant genetic component. Current evidence supports the hypothesis that gene variation causes a predisposition to the disease. In 2003, we initiated this project by recruiting advanced AMD patients and age-control individuals with normal retinas. Up to date, 373 individuals have been enrolled and 60 histopathological cases with AMD have been collected. We also received and analyzed 835 DNA samples from the Blue Mountain Eye Study in Australia and 534 DNA samples 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 studies of these SNPs by in vitro and/or in vivo experiments. Through this approach, we can 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 the above experiments and recent literature, a genetically engineered animal has been generated to act as the disease model. In FY2008, we have accomplished the following: (1) established an new platform for more efficient SNP typing, (2) completed the study on HtrA1 SNP-environmental interaction and published the paper in Ophthalmology, (3) further characterization of the retinal lesions in Ccl2/Cx3cr1 double knock-out (DKO) mice - a murine model of AMD, (4) completed to test the effect of long-chain omega-3 fatty acid on the retinal lesions of the DKO mice, a manuscript is prepared for submission, (5) started to investigate the the possible involvement of mitochondria in the AMD pathogenesis using in vitro and in vivo models, (6) reported differential expression of ERp29 in retinal pigment epithelial cells of DKO and wild type mice, and published a paper in Current Eye Research.
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