The effect of hyaluronic acid on corneal epithelial cell proliferation.
OBJECTIVE
The authors investigated the mechanisms by which hyaluronic acid (HA) promotes corneal epithelial wound healing. The effect of HA on epithelial cell proliferation was examined in comparison with that of epidermal growth factor (EGF) and fibronectin (FN).


METHODS
A penetrating linear incision (6-mm long) was made in the center of rabbit corneas. Immediately after wounding, the corneas were excised and cultured in TCM199 medium alone or medium containing HA (molecular weight, 860,000 Daltons; 100, 400, or 1000 micrograms/ml), EGF (25, 100, or 250 ng/ml), or FN (100 or 250 micrograms/ml) for 15 hr at 37 degrees C. The corneas were then labeled with tritiated thymidine (10 microCi/ml) and subjected to autoradiography.


RESULTS
In the corneas cultured with HA at concentrations of 400 and 1000 micrograms/ml, the number of epithelial cells incorporating tritiated thymidine was significantly higher than that in the control corneas. In the corneas cultured with EGF at all concentrations, it was also higher than that of the control. FN did not affect cell proliferation.


CONCLUSIONS
HA stimulates corneal epithelial cell proliferation. This stimulating effect of HA on epithelial cell proliferation might partly explain its effect in promoting corneal epithelial wound healing.
Department of Ophthalmology, School of Medicine, Kobe University, Japan.
M
M
Inoue
C
C
Katakami
D000818:Animals; D001345:Autoradiography; D002455:Cell Division / Q000187:drug effects; D003315:Cornea / Q000187:drug effects* / Q000473:pathology; D065306:Corneal Injuries; D004261:DNA Replication; D004815:Epidermal Growth Factor / Q000494:pharmacology; D004848:Epithelium / Q000187:drug effects / Q000293:injuries / Q000473:pathology; D005353:Fibronectins / Q000494:pharmacology; D006820:Hyaluronic Acid / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011817:Rabbits; D013936:Thymidine / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D005353:Fibronectins; D004815:Epidermal Growth Factor; D006820:Hyaluronic Acid; D013936:Thymidine