The long-term effect of tacrolimus on alkali burn-induced corneal neovascularization and inflammation surpasses that of anti-vascular endothelial growth factor

Abstract

Purpose

To investigate the effect of tacrolimus in alkali burn-induced corneal neovascularization (NV) and inflammation and to compare with anti-vascular endothelial growth factor (anti-VEGF).

Methods

After corneal alkali-burn, 84 Wistar rats were randomly divided into three groups and received either saline solution or 0.05% tacrolimus (0.5 mg/mL) four times daily, or subconjunctival anti-VEGF injection (0.5 mg/0.05 mL). Corneal NV, opacity and epithelial defects, the status of inflammation, and the levels of proinflammatory and angiogenic cytokines were assessed on Days 3, 7, 14 and 28 post-injury.

Results

Compared with the control, tacrolimus significantly reduced corneal NV on Days 7, 14 and 28 post-injury, and anti-VEGF significantly reduced corneal NV at each assessment. Nevertheless, the tacrolimus group had significantly less corneal NV than the anti-VEGF group on Days 14 and 28. Furthermore, both tacrolimus and anti-VEGF significantly decreased the VEGF-A expression on Days 7 and 14, with no significant difference between the two groups. Moreover, corneal inflammatory response was alleviated, and corneal opacity and epithelial defects were significantly reduced by tacrolimus. Additionally, the expression of IL-1β, IL-6, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and TGF-β were significantly decreased by tacrolimus.

Conclusion

Our findings suggested that 0.05% tacrolimus suspension eye drops effectively reduced alkali burn-induced corneal NV and inflammation, with a better effect than subconjunctival anti-VEGF injections on Days 14 and 28.