Effects of Tranilast on Cultured Rabbit Corneal Keratocytes and Corneal Haze After Photorefractive Keratectomy

Abstract

Purpose: In vitro and in vivo studies were performed to elucidate the effects of tranilast on cellular proliferation and collagen synthesis. Methods: Subculturing was carried out using keratocytes from rabbits that underwent photorefractive keratectomy (PRK) and developed corneal haze, and keratocytes from normal rabbit cornea. Results: Tranilast suppressed proliferation in cultured keratocytes from the corneal haze region at doses of 30 and 300 μmol/L and collagen synthesis at doses of 3, 30, and 300 μmol/L. Normal corneal cultures showed suppression of keratocyte proliferation and collagen synthesis only at a high dose of tranilast (300 μmol/L). Betamethasone suppressed proliferation of keratocytes in both haze and normal cornea at a dose of 10 μmol/L, as well as collagen synthesis at respective doses of 1 and 10 μmol/L. Diclofenac sodium suppressed collagen synthesis of keratocytes in haze cornea at a high dose of 100 μmol/L, and in keratocytes in normal cornea, at doses of 10 and 100 μmol/L. In an in vivo study, either 0.5% tranilast, 0.1% betamethasone phosphate eye drops, or a tranilast base solution (control) was instilled four times daily to rabbits that had undergone PRK. Weekly evaluation of the inhibitory effect of these drugs on the development of haze was performed 2 weeks after surgery. Tranilast suppressed haze 6–13 weeks after PRK, but betamethasone phosphate showed no effect. Conclusion: These results indicate that tranilast is potentially effective for inhibiting the corneal haze that occurs after PRK.