Abstract
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.
Highlights
Chemical injury of the eye is a common intractable ocular disease in the clinic
Representative pictures of the injured corneas are shown in Figure 1(a). e corneal opacity score was lower in the doxycycline group than in the control group 7 and 14 days after chemical injury (P < 0.05) (Figure 1(b))
Real-time PCR showed that the levels of transforming growth factor-β1 (TGF-β1) mRNA were lower in the doxycycline group than in the control group 3, 7, and 14 days after corneal alkali burn (P < 0.05) (Figure 3(a))
Summary
Chemical injury of the eye is a common intractable ocular disease in the clinic. Slow epithelialization, persistent ulceration, corneal perforation, neovascularization (NV), and opacification are the main complications, and chemical injury of the eye may cause permanent visual impairment or blindness [1, 2]. Keratocyte activation, myofibroblast formation, and tissue fibrosis all participate in the wound healing process or scar formation in the cornea after alkali burn [3, 4]. Normal corneal keratocytes are stationary and help maintain corneal transparency; after corneal injury, the disruption of corneal integrity induces quiescent keratocytes to differentiate into active myofibroblasts [5]. TGF-β1 has been shown to be upregulated and induce the differentiation of keratocytes to myofibroblasts, which contributes to the recovery of the cornea [9, 10]. TGF-β1 has been found to stimulate the expression of MMP-9 in the cornea [13]. NF-κB competes with TGF-β1 to control the expression of MMPs [14], and the degradation of the basement
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