Myopia is an extremely pervasive abnormality of vision that is usually caused by excessive growth of the posterior part of the eye relative to the optical power of the cornea and lens. The cumulative cost of myopia and its treatment is huge. The onset and progression of myopia are strongly influenced by environmental factors, but the risk of becoming myopic is clearly influenced by genes. The central aim of this work is to determine what genes and molecules normally regulate the growth of different parts of the mammalian eye and to then assess whether any of these same genes contribute to optical abnormality in humans.
The first aim of this project is to systematically map genes that selectively influence the growth of the eye, the lens, the cornea, and the retina of mice. Using novel quantitative trait locus (QTL) interval mapping methods, more than 10 gene loci that selectively affect the growth of different parts of the eye will be mapped with F2 intercrosses. As part of the second aim, these QTLs will be mapped with far greater precision (a critical region of 1‑2 cM) using special mapping resources‑advanced intercrosses and reciprocal congenic lines. Complementary methods will then be used to evaluate the most promising candidate genes linked with particular QTLs.
The third aim i s a developmental study of the mekics of eye growth in several important strains, and in specially engineered congenic strains. This work will test ideas about how genes and environmental factors affect the optics of eye development. Understanding how different QTLs affect different parts of the eye will ultimately contribute to a far better understanding of molecular and developmental mechanisms associated with eye growth in humans.
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