Retinal diseases such as retinal detachments and macular degeneration are a leading cause of vision loss and blindness in this country and around the world. Despite available surgical and medical treatments for these diseases, patients still experience a large amount of vision loss secondary to the disruption in nutritional support provided to the retina by the underlying tissues. This disruption causes death of the retina, and of the photoreceptor cells in particular. Apoptosis, or programmed cell death, has been implicated as the mechanism by which photoreceptor cells die, but the molecular mechanisms of activation, transduction and execution of the apoptotic cascade in retinal diseases are poorly understood. The main hypothesis of this research proposal is that photoreceptor cell death during retinal detachments and macular degeneration occurs via apoptosis. The research outlined in this application will use a newly developed rodent model of retinal detachments and molecular biologic and genetic techniques to gain new insight into apoptotic photoreceptor cell death. This will allow us to develop and test new neuroprotective therapies for improving visual outcomes in retinal disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08EY014705-05
Application #
7118937
Study Section
Special Emphasis Panel (ZEY1-VSN (02))
Program Officer
Mariani, Andrew P
Project Start
2002-09-30
Project End
2008-08-31
Budget Start
2006-09-01
Budget End
2008-08-31
Support Year
5
Fiscal Year
2006
Total Cost
$202,536
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
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Zadro-Lamoureux, Laura A; Zacks, David N; Baker, Adam N et al. (2009) XIAP effects on retinal detachment-induced photoreceptor apoptosis [corrected]. Invest Ophthalmol Vis Sci 50:1448-53
Zacks, David N; Boehlke, Christopher; Richards, Ayo-Lynn et al. (2007) Role of the Fas-signaling pathway in photoreceptor neuroprotection. Arch Ophthalmol 125:1389-95
Zacks, David N; Han, Ying; Zeng, Yong et al. (2006) Activation of signaling pathways and stress-response genes in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci 47:1691-5
Zacks, David N; Zheng, Qiong-Duan; Han, Ying et al. (2004) FAS-mediated apoptosis and its relation to intrinsic pathway activation in an experimental model of retinal detachment. Invest Ophthalmol Vis Sci 45:4563-9