Inhibition of Apoptosis in Experimental Glaucoma

Stuart McKinnon, MD, PhD
Duke University (Durham, NC)
Year Awarded:
2000
Grant Duration:
April 1, 2000 to March 31, 2002
Disease:
Glaucoma
Award Amount:
$50,000
Grant Reference ID:
G2000008
Award Type:
Standard
Award Region:
US Southern

Inhibition of Apoptosis in Experimental Glaucoma

Details


In glaucoma, the loss of retinal ganglion cells (RGC) proceeds by a mechanism known as apoptosis. Apoptosis is an organized, or programmed, form of cell death that requires the action of a series of proteases (proteins that chop up other proteins) called caspases. In animal models of glaucoma, the protease Caspase-3 is found to be activated in RGCs, where it also cleaves a molecule called amyloid precursor protein (APP). APP is important in Alzheimer's disease (AD) as well as in glaucoma. In fact, the excessive production of smaller fragments of APP, called amyloid beta, is a hallmark of AD and is thought to be toxic to neurons. Dr. McKinnon is interested in the fact that these two different neurodegenerative diseases, glaucoma and AD, share some key features. He is examining the apoptotic death of RGCs and the possible role of APP in more detail. An understanding of RGC apoptosis could be important in devising protective strategies for preventing glaucomatous damage, and these studies may also illuminate general features of nerve cell death in the central nervous system, making them relevant to other neurodegenerative diseases like AD.

Publications

McKinnon, S.J., Lehman, D.M., Kerrigan-Baumrind, L.A., Merges, C.A., Pease, M.E., Kerrigan, D.F., Ransom, N.L., Tahzib, N.G., Reitsamer, H.A., Levkovitch-Verbin, H., Quigley, H.A., and Zack, D.J. (2002) Caspase activation and amyloid precursor protein cleavage in rat ocular hypertension. Invest Ophthalmol. Vis. Sci. 43(4):1077-1087.  

McKinnon, S.J., Lehman, D.M., Tahzib, N.G., Ransom, N.L., Reitsamer, H.A., Liston, P., LaCasse, E., Li, Q., Korneluk, R.G., and Hauswirth, W.W. (2002) Baculoviral IAP repeat-containing-4 protects optic nerve axons in a rat glaucoma model. Molecular Therapy. 5(6):780-787.  

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