Understanding genes that control corneal thickness

Michael Anderson, PhD
University of Iowa (Iowa City, IA)
Year Awarded:
2007
Grant Duration:
April 1, 2007 to March 31, 2009
Disease:
Glaucoma
Award Amount:
$90,000
Grant Reference ID:
G2007064
Award Type:
Standard
Award Region:
US Midwestern
Recipient of the Thomas R. Lee Award for glaucoma research

Genetics of Central Corneal Thickness in Mice

Summary

Corneal thickness has been implicated in risk for glaucoma. This study seeks to determine whether corneal thickness is genetically controlled.

Details


The cornea is the outermost covering of the eye. Given the importance of the cornea to vision, it is somewhat surprising that the cornea exhibits vast person-to-person variability, especially regarding its overall thickness (referred to as central corneal thickness, CCT). Recently, it has become clear that differences in CCT are more than a mere anatomical curiosity. CCT strongly associates with several ocular diseases, particularly glaucoma. The Ocular Hypertension Treatment Study (OHTS, a large, multicenter, prospective clinical glaucoma study) recently found that a thinner CCT predicts the development of primary open angle glaucoma. The pathophysiological reason for this association remains unknown. Our experiments offer an innovative approach that will allow CCT to be studied at the molecular level using experiments with mice. Knowing the genes that influence CCT, even in mice, will immediately suggest new mechanistic hypotheses that can be carried back into human studies. Our work also addresses an important health disparity issue that exists among patients with glaucoma. Advancing age and elevated intraocular pressure are two well known risk factors for developing glaucoma. Race is another. Both the incidence of glaucoma and the incidence of thin corneas are much more common among African Americans than other ethnicities. For unknown reasons, African Americans with glaucoma have on average more severe disease that is more resistant to treatment in comparison to patients of other ethnicities. The reason for these associations may in part reflect the biological connections that link CCT and glaucoma. Our studies in mice offer an innovative approach for identifying molecules influencing CCT and experimentally testing their relevance to glaucoma. Ultimately, results of these studies will contribute to an improved understanding of the risk factors that contribute to glaucoma, with the long term goal being the development of improved therapies and outcomes for all people affected by glaucoma.

Publications

Anderson, M.G., Hawes, N.L., Chang, B., Petersen, G.E., Jiang, B., and Lively, G. Genetic dissesction of central corneal thickness utilizing inbred strains of mice. Abstract accepted for presentation at the Association for Research in Vision and Ophthalmology 2008 Annual Meeting, April 27-May 1 in Fort Lauderdale, Florida. [conference abstract] Lively, G.D., Jiang, B., Hedberg-Buenz, A., Chang, B., Petersen, G.E., Kuehn, M.H. Wang, K., and Anderson, M.G. (2009) Genetic Dependence of Central Corneal Thickness among Inbred Strains of Mice. Investigative Ophthalmology and Visual Science  

Lively GD, Koehn D, Hedberg-Buenz A, Wang K, Anderson MG. Quantitative trait loci associated with murine central corneal thickness. Physiol Genomics. 2010 Jul 7;42(2):281-6. Epub 2010 Apr 27.  

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