October 1990
Volume 31, Issue 10
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Articles  |   October 1990
Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin.
Author Affiliations
  • R J Cenedella
    Department of Biochemistry, Kirksville College of Osteopathic Medicine, Missouri 63501.
  • C R Fleschner
    Department of Biochemistry, Kirksville College of Osteopathic Medicine, Missouri 63501.
Investigative Ophthalmology & Visual Science October 1990, Vol.31, 1957-1962. doi:https://doi.org/
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      R J Cenedella, C R Fleschner; Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin.. Invest. Ophthalmol. Vis. Sci. 1990;31(10):1957-1962. doi: https://doi.org/.

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Abstract

The authors developed a direct chemical approach for estimating the rate of turnover of the corneal epithelium in vivo. The method was used to examine the effects of lovastatin, a potent inhibitor of cholesterol biosynthesis, on proliferation and turnover of the epithelium. Corneal DNA was labeled by pulse injection (IP) of the rat with 3H-thymidine, and 3H-labeled DNA was recovered from peripheral and central corneas over the next 15 days. Only the epithelium became labeled, and the loss of label by cell desquamation began 3 days after injection. The loss of 3H-DNA from the cornea (peripheral plus central region) followed first-order kinetics. The half-life of the disappearance was about 3 days. The peripheral cornea became more highly labeled than the central cornea and began to lose 3H-DNA before the central cornea. These observations support the possibility of a higher mitotic rate in the peripheral region and the centripetal movement of a population of peripheral epithelial cells in the normal cornea. The half-lives of the disappearance of 3H-DNA from peripheral and central corneas measured between days 5 and 15 postinjection were identical, both at 3 days. Complete turnover of the corneal epithelium would, therefore, require about 2 weeks (4-5 half-lives). Treatment of the rat with lovastatin had no obvious effects upon the proliferation or turnover of the corneal epithelium. Although lovastatin inhibited corneal 3-hydroxy-3-methylglutaryl coenzyme A reductase, the key regulatory enzyme of cholesterol synthesis, the cornea compensated by induction of this enzyme so that there was no net inhibition of cholesterol synthesis in the cornea.

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