This grant proposal outlines a five-year training program for the development of an academic career in molecular biology. The principal investigator is a fellowship-trained clinician who proposes to expand and diversify his scientific ability through intensive coursework and reentered research training. The didactic portion of this program will consist of graduate level coursework at Duke University and regular sessions with the proposed mentors, Drs Klintworth and Bowes Rickman. Dr Klintworth is director of the Ophthalmic Genetics Center at Duke University and has expertise in studying genetically determined diseases of the eye. Dr Bowes Rickman is an Assistant Professor of Ophthalmology and Cell Biology and has expertise in characterizing mRNAs and proteins in ocular disorders. The proposed research is to investigate the molecular mechanisms that are associated with the development of pseudoexfoliation syndrome (PEX) and pseudoexfoliation syndrome with glaucoma (PEX-G) using gene array technologies. PEX is an idiopathic systemic disease characterized by fibrillar deposits in multiple ocular and non-ocular tissues. PEX is the most common identifiable cause of open angle glaucoma worldwide and is phenotypically distinct from primary open angle glaucoma. Growing evidence suggests that PEX is a late onset inherited disorder. Despite the prevalence of PEX and PEX-G little is known about their underlying molecular mechanisms. In short, we propose to: 1) Identify genes or ESTs involved in the pathogenesis of PEX using gene array technologies 2) Characterize/deduce gene sequences 3) Identify differences in gene expression between PEX and PEX-G and 4) Ascertain and recruit additional PEX patients and families. These investigations are critical to understanding the molecular basis of PEX and any modifying genetic factors that would predispose to the development of glaucoma. The Ophthalmology department at Duke University is an ideal setting for training physician-scientists and has an established track record of strong support for promising clinician-scientists.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23EY014019-03
Application #
6937089
Study Section
Special Emphasis Panel (ZEY1-VSN (08))
Program Officer
Liberman, Ellen S
Project Start
2003-09-01
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
3
Fiscal Year
2005
Total Cost
$186,125
Indirect Cost
Name
Duke University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Huang, Wei; Li, Guorong; Qiu, Jianming et al. (2013) Protective effects of resveratrol in experimental retinal detachment. PLoS One 8:e75735
Li, Guorong; Luna, Coralia; Navarro, Iris D et al. (2011) Resveratrol prevention of oxidative stress damage to lens epithelial cell cultures is mediated by forkhead box O activity. Invest Ophthalmol Vis Sci 52:4395-401
Khan, Tanya T; Li, Guorong; Navarro, Iris D et al. (2010) LOXL1 expression in lens capsule tissue specimens from individuals with pseudoexfoliation syndrome and glaucoma. Mol Vis 16:2236-41
Luna, Coralia; Li, Guorong; Liton, Paloma B et al. (2009) Resveratrol prevents the expression of glaucoma markers induced by chronic oxidative stress in trabecular meshwork cells. Food Chem Toxicol 47:198-204
Challa, Pratap (2009) Genetics of pseudoexfoliation syndrome. Curr Opin Ophthalmol 20:88-91
Liu, Yutao; Akafo, Stephen; Santiago-Turla, Cecile et al. (2008) Optineurin coding variants in Ghanaian patients with primary open-angle glaucoma. Mol Vis 14:2367-72
Liu, Xialin; Zhang, Min; Liu, Yuhua et al. (2008) Proteomic analysis of regenerated rabbit lenses reveal crystallin expression characteristic of adult rabbits. Mol Vis 14:2404-12
Liu, Yutao; Schmidt, Silke; Qin, Xuejun et al. (2008) Lack of association between LOXL1 variants and primary open-angle glaucoma in three different populations. Invest Ophthalmol Vis Sci 49:3465-8
Challa, Pratap; Schmidt, Silke; Liu, Yutao et al. (2008) Analysis of LOXL1 polymorphisms in a United States population with pseudoexfoliation glaucoma. Mol Vis 14:146-9
Challa, Pratap (2008) Glaucoma genetics. Int Ophthalmol Clin 48:73-94

Showing the most recent 10 out of 16 publications