Although vision loss in primary open angle glaucoma (POAG) results from retinal ganglion cell (RGC) death, the mechanistic basis for early and progressive RGC loss is unknown. With the aging population and increasing prevalence of glaucoma, there is an urgent need to elucidate the pathophysiology of RGC loss at both the molecular and cellular levels to develop medications that specifically address RGC loss in treating POAG patients. My research goal is to identify a molecular pathway by studying how RGC loss result from mutations in optineurin, which has been associated with familial normal pressure POAG in human genetic studies. We will investigate optineurin's novel role in regulating NF-:B activity and determine how mutations alter its normal function. The data from this research proposal are expected to reveal a defective biochemical pathway that lead to RGC death, which will facilitate the identification of specific targets for developing novel therapeutic or diagnostic approaches in POAG.

Public Health Relevance

Glaucoma patients ultimately become blind from loss of retinal ganglion cells (RGCs), but how and why RGCs die are unknown. This translational laboratory research study will specifically investigate this process by studying a protein called optineurin, which causes normal pressure primary open angle glaucoma when patients inherit a mutation. The results can lead to medical insights into developing new drugs or new methods of early glaucoma detection in the clinics.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08EY021520-03
Application #
8509701
Study Section
Special Emphasis Panel (ZEY1-VSN (10))
Program Officer
Agarwal, Neeraj
Project Start
2011-09-30
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$175,905
Indirect Cost
$13,030
Name
Duke University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705