department of pharmacology

Timothy Kern, Ph.D.

kern

Professor
Director of the Center for Diabetes Research

Director of the Center for Diabetes Research

W441
School of Medicine
2109 Adelbert Rd.
Case Western Reserve University

Mailing Address:
10900 Euclid Ave.
Cleveland, Ohio 44106-4951

Phone: (216) 368-0800
Fax: (216) 368-5824
E-mail: tsk@case.edu

Research

The major focus of research in our laboratory is to learn what causes retinopathy in diabetes, and how it can be prevented. Diabetic retinopathy takes many years to develop in most patients, so studies using research animals have been fundamental to our present understanding of this retinopathy. The retinal lesions that develop in diabetic animals are indistinguishable from those that develop in patients, and include microaneurysms, obliterated capillaries, pericyte loss and hemorrhage. We have also developed a second model of diabetic retinopathy in which blood hexose levels are elevated in nondiabetic animals by feeding the sugar, galactose. These animals develop a retinopathy identical to that which develops in diabetes, indicating that elevated blood hexose is a major cause of diabetic retinopathy.

Efforts in our laboratory currently are directed primarily at identifying how hyperglycemia causes retinopathy, so that new, improved treatment may be devised to inhibit the loss of vision in diabetes. Two hyperglycemia-induced abnormalities of retinal metabolism presently are being investigated in our lab; non-enzymatic attachment of hexose to proteins, lipids and nucleotides, and activation of protein kinase C activity. Therapies that correct these metabolic abnormalities are being investigated to determine the relationship of retinal dysmetabolism to tissue function and the development of retinopathy and other forms of microvascular disease.

SELECTED REFERENCES:


Du, Y., Smith, M.A., Miller, C.M., Kern, T.S. 2002, Diabetes-induced nitrative stress in the retina, and correction by aminoguanidine. J. Neurochem. 80:771-79.

Mohr, S., Tang, J., Kern, T.S., 2002, Caspase activiation in retinas of diabetic and galactosemic mice and diabetic patients. Diabetes 5:1172-79.

Ishii, H., Jirousek, M.R., Koya, D., Takagi, C., Xia, P., Clermont, A., Bursell, S-E., Kern, T.S., Ballas, L.M., Heath, W.F., Stramm, L.E., Feener, E.P., King, G.L. 1996. Amelioration of vascular dysfunctions in diabetic rats by an oral PKC b inhibitor. Science, 272:728-731.

Kern, T.S. and Engerman, R.L. (2001) Pharmacologic inhibition of diabetic retinopathy: Aminoguanidine and aspirin. Diabetes 50, 1636-42.