Timothy Kern, Ph.D.
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.