Kinetics of corneal epithelium turnover in vivo. Studies of lovastatin

Journal Article · Mon Oct 01 00:00:00 EDT 1990 · Investigative Ophthalmology and Visual Science; (USA)

OSTI ID:6272837

Cenedella, R J; Fleschner, C R ^[1]

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1. Kirksville College of Osteopathic Medicine, MO (USA)

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.

• OSTI ID: 6272837
• Journal Information: Investigative Ophthalmology and Visual Science; (USA), Journal Name: Investigative Ophthalmology and Visual Science; (USA) Vol. 31:10; ISSN 0146-0404; ISSN IOVSD
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL TISSUES
ANIMALS
AZINES
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL HALF-LIFE
BIOSYNTHESIS
BODY
BODY AREAS
CELL PROLIFERATION
CHOLESTEROL
CORNEA
DISTRIBUTION
DNA
ENZYME INHIBITORS
ENZYMES
EPITHELIUM
EYES
FACE
HEAD
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IN VIVO
KINETICS
MAMMALS
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
OXIDOREDUCTASES
PYRIMIDINES
RATS
REACTION KINETICS
RIBOSIDES
RODENTS
SENSE ORGANS
STEROIDS
STEROLS
SYNTHESIS
THYMIDINE
TISSUE DISTRIBUTION
TISSUES
TRITIUM COMPOUNDS
VERTEBRATES