Over 100 million Americans suffer from some type of visual impairment, and genetic disorders account for more than 95 percent of common eye diseases. Although advances in molecular genetics are rapidly increasing the identification of the genes underlying human ocular disorders, studying the natural history of eye disorders and the complex genetics involved requires experimental models. This project is a highly productive collaboration between ophthalmologists and mammalian geneticists in which clinically-relevant mouse models of ocular disease are identified and then characterized with gene mapping and documentation of the disease process. The mouse eye is structurally very similar to the human eye; defined genetics can be done and disease processes are easily studied. The mouse and human genomes share large conserved regions, and genes mapped or cloned in the mouse have a high likelihood of giving important information for human disease as well.
The specific aims of this project are to screen for ocular abnormalities in mice from inbred and mutant strains and stocks at The Jackson laboratory (TJL). For each new disorder we determine if the trait is genetically transmitted; document the natural disease course by employing clinical and basic science methods, and perform genetic studies to determine the inheritance pattern, confirm that the expressed phenotype is new and unique, and identify chromosomal location. Candidate genes that map near eye mutations are tested for selected mutations. Methods include screening for rod and cone dystrophies employing a new photopic electroretinogram protocol, and obtaining high quality fluorescein angiograms for neovascularization. Comprehensive genetic studies and basic characterization will be performed at TJL. Detailed analysis of retinal mutants by electroretinography, histology and clinical characterization will be performed at the Harbor-UCLA Research and Education Institute. To bridge the two locations and to provide coordination to the project, Dr. Heckenlively works at TJL four times a year or about 24 to 30 days annually.
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