Timothy S. Kern, Ph.D.
Professor of Medicine(Clinical & Molecular Endocrinology)
Director of the Center for Diabetes Research
Biomedical Research Building, 434
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.