Concentration and molecular weight dependency of rabbit corneal epithelial wound healing on hyaluronan

Hyaluronan (hyaluronic acid) is a high molecular weight viscoelastic polymer which has been postulated to enhance wound healing. We investigated the dose and molecular weight (9 x 10(4)-280 x 10(4) dependent effects of hyaluronan on the rate of migration of rabbit corneal epithelium in organ culture and on wound closure in vivo after debridement with n-heptanol. When corneal blocks were cultured with hyaluronan for 20 hours, distances of epithelial migration significantly increased over exposed stroma in proportion to hyaluronan concentration. However, there was no difference in the stimulatory action of hyaluronan on epithelial migration when corneal blocks were cultured at 1 mg/ml of hyaluronan irrespective of changes in the molecular weight range between 9 x 10(4) and 280 x 10(4). Glycosaminoglycans other than hyaluronan (chondroitin, chondroitin sulfate, keratan sulfate and heparan sulfate) failed to increase the epithelial migration. When hyaluronan eye drops were instilled after corneal epithelial removal with n-heptanol, hyaluronan stimulated wound closure in a dose-dependent manner, but its stimulatory efficacy was not dependent on molecular weight.