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.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY012991-04
Application #
6658958
Study Section
Visual Sciences B Study Section (VISB)
Program Officer
Chin, Hemin R
Project Start
2000-09-01
Project End
2004-07-31
Budget Start
2003-08-10
Budget End
2004-07-31
Support Year
4
Fiscal Year
2003
Total Cost
$284,000
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Pardue, Machelle T; Faulkner, Amanda E; Fernandes, Alcides et al. (2008) High susceptibility to experimental myopia in a mouse model with a retinal on pathway defect. Invest Ophthalmol Vis Sci 49:706-12
Simon, Perikles; Schott, Klaus; Williams, Robert W et al. (2004) Posttranscriptional regulation of the immediate-early gene EGR1 by light in the mouse retina. Eur J Neurosci 20:3371-7
Jablonski, Monica M; Lu, Lu; Wang, XiaoFei et al. (2004) The ldis1 lens mutation in RIIIS/J mice maps to chromosome 8 near cadherin 1. Mol Vis 10:577-87
Schaeffel, Frank; Burkhardt, Eva; Howland, Howard C et al. (2004) Measurement of refractive state and deprivation myopia in two strains of mice. Optom Vis Sci 81:99-110
Seecharan, Dave J; Kulkarni, Anand L; Lu, Lu et al. (2003) Genetic control of interconnected neuronal populations in the mouse primary visual system. J Neurosci 23:11178-88
Pollock, Graeme S; Robichon, Regine; Boyd, Kristina A et al. (2003) TrkB receptor signaling regulates developmental death dynamics, but not final number, of retinal ganglion cells. J Neurosci 23:10137-45
Schaeffel, Frank; Simon, Perikles; Feldkaemper, Marita et al. (2003) Molecular biology of myopia. Clin Exp Optom 86:295-307
Zhou, G; Strom, R C; Giguere, V et al. (2001) Modulation of retinal cell populations and eye size in retinoic acid receptor knockout mice. Mol Vis 7:253-60
Cook, M N; Williams, R W; Flaherty, L (2001) Anxiety-related behaviors in the elevated zero-maze are affected by genetic factors and retinal degeneration. Behav Neurosci 115:468-76