The Wound Healing Effect of Doxycycline after Corneal Alkali Burn in Rats

PURPOSE: To evaluate the wound healing effect of doxycycline and its underlying mechanisms in a rat model of corneal alkali burn. METHODS: Male SD rats were administered 1.0 N NaOH in the right cornea for 25 seconds and randomly divided into the doxycycline group and the control group, with 84 rats in each group. 1.0 g·L(−1) doxycycline eye drops (doxycycline group) or vehicle (control group) was topically instilled onto the rat cornea after chemical injury. Three days, 7 days, and 14 days after alkali burn, microscopy was used to observe corneal wound healing by fluorescein staining and the degree of corneal opacity. The expression of transforming growth factor-beta 1 (TGF-β1) and matrix metalloproteinase-9 (MMP-9) was detected by RT-PCR and ELISA, alpha-smooth muscle actin (a-SMA) levels were measured by immunofluorescent staining, and Western blot assays for TGF-β1, a-SMA, and nuclear factor-kappa B (NF-κB) were also performed. RESULTS: Corneal wound healing and corneal opacity scores were better in the doxycycline group than in the control group. Three, 7, and 14 days after corneal alkali burn, a significant increase in TGF-β1 was observed in corneas from the control group, compared with the corneas from the doxycycline group (P < 0.05). The corneal levels of MMP-9 in the doxycycline group were lower than those in the control group 3 days and 7 days after alkali burn (P < 0.05). In addition, doxycycline inhibited α-SMA expression and suppressed NF-κB expression. CONCLUSION: Doxycycline treatment promoted corneal healing and reduced corneal opacity in SD rats. Doxycycline protected the cornea from alkali burn injury by reducing TGF-β1, MMP-9, NF-κB, and α-SMA expression.