Abstract

This proposal is based upon the hypothesis that evaluation of changes in gene expression in response to specific stimuli will lead to identification of glaucoma genes that are involved in loss of intraocular pressure homeostasis. By utilizing the known glaucoma gene, TIGR, and evaluating the response of gene expression in relation to changes in TIGR levels, the PI anticipates that additional glaucoma genes will be identified.
Four specific aims are outlines. The first will use microarray technology to establish expression profiles of human trabecular meshwork cells (HTM) in response to aqueous, glaucoma medications and other inducing agents.
The second aim will analyze genes identified in aim 1 that may be a part of a pathway including TIGR and place the gene upstream or downstream of TIGR.
The third aim will determine which of the genes identified in specific aim 1 map to glaucoma locus genetic inclusion intervals. These genes will be screened for mutations in glaucoma and control populations. The final specific aim will carry out genotype/phenotype studies of TIGR and newly identified glaucoma genes. The long term goal of this lab is to elucidate the underlying causes of glaucoma and the accompanying pathogenic processes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY009580-09
Application #
6334653
Study Section
Special Emphasis Panel (ZRG1-SSS-R (03))
Program Officer
Liberman, Ellen S
Project Start
1992-09-30
Project End
2006-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
9
Fiscal Year
2001
Total Cost
$589,413
Indirect Cost

  Institution

Name
University of Michigan Ann Arbor
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109

  Publications

Bailey, Jessica N Cooke; Gharahkhani, Puya; Kang, Jae H et al. (2018) Testosterone Pathway Genetic Polymorphisms in Relation to Primary Open-Angle Glaucoma: An Analysis in Two Large Datasets. Invest Ophthalmol Vis Sci 59:629-636
Khawaja, Anthony P; Cooke Bailey, Jessica N; Wareham, Nicholas J et al. (2018) Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. Nat Genet 50:778-782
Pasquale, Louis R (2016) Vascular and autonomic dysregulation in primary open-angle glaucoma. Curr Opin Ophthalmol 27:94-101
Li, Zheng; Allingham, R Rand; Nakano, Masakazu et al. (2015) A common variant near TGFBR3 is associated with primary open angle glaucoma. Hum Mol Genet 24:3880-92
Kang, J H; Loomis, S J; Yaspan, B L et al. (2014) Vascular tone pathway polymorphisms in relation to primary open-angle glaucoma. Eye (Lond) 28:662-71
Springelkamp, Henriët; Höhn, René; Mishra, Aniket et al. (2014) Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. Nat Commun 5:4883
Loomis, Stephanie J; Kang, Jae H; Weinreb, Robert N et al. (2014) Association of CAV1/CAV2 genomic variants with primary open-angle glaucoma overall and by gender and pattern of visual field loss. Ophthalmology 121:508-16
Garnai, Sarah J; Huyghe, Jeroen R; Reed, David M et al. (2014) Congenital cataracts: de novo gene conversion event in CRYBB2. Mol Vis 20:1579-93
Liu, Yutao; Garrett, Melanie E; Yaspan, Brian L et al. (2014) DNA copy number variants of known glaucoma genes in relation to primary open-angle glaucoma. Invest Ophthalmol Vis Sci 55:8251-8
Bailey, Jessica N Cooke; Yaspan, Brian L; Pasquale, Louis R et al. (2014) Hypothesis-independent pathway analysis implicates GABA and acetyl-CoA metabolism in primary open-angle glaucoma and normal-pressure glaucoma. Hum Genet 133:1319-30

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