Investigative Ophthalmology & Visual Science, Vol 34, 2105-2111, Copyright © 1993 by Association for Research in Vision and Ophthalmology

ARTICLES AND REPORTS

Stimulation of DNA synthesis and c-fos expression in corneal endothelium by insulin or insulin-like growth factor-I

ST Feldman, D Gately, BL Seely, A Schonthal and JR Feramisco
Department of Ophthalmology, University of California, San Diego School of Medicine.

PURPOSE. To study the growth regulation of bovine corneal endothelium, the effects of insulin and insulin-like growth factor-I on the expression of the c-fos proto-oncogene as well as on DNA synthesis were analyzed. Bovine corneal endothelial cells were also analyzed for the presence of insulin and insulin-like growth factor-I receptors. METHODS. Indirect immunofluorescence was used to assess the effect of stimulation by insulin and insulin-like growth factor-I on c-fos protein expression and DNA synthesis quiescent bovine corneal endothelium. Receptor number was determined by 125I-insulin or 125I-IGF- I binding studies. RESULTS. Fetal bovine serum strongly stimulated c- fos protein expression and DNA synthesis. Insulin-like growth factor-I was less effective while insulin was effective only at high concentrations. Scatchard analysis of 125I-insulin-like growth factor-I and 125I-insulin binding to bovine corneal endothelium revealed 180,000 IGF-I receptors and 7,000 insulin receptors. CONCLUSION. The number of insulin-like growth factor-I receptors far exceeds the number of insulin receptors in bovine corneal endothelium, suggesting that the effects of insulin on c-fos gene expression and mitogenesis were likely to be mediated through the insulin-like growth factor-I receptor.