Comparative Study of Tacrolimus and Bevacizumab on Corneal Neovascularization in Rabbits

Abstract

PurposeTo compare the anti‐angiogenic effects of tacrolimus and bevacizumab on corneal neovascularization in rabbits.MethodsNeovascularization was induced in 32 eyes of 16 rabbits by placing suture in the corneal stroma. Seven days after suture placement, all rabbits were divided into four groups and were treated subconjunctivally with bevacizumab 0.05 mL (5 mg/0.05 mL; AVA_sub), Tacrolimus 0.05 mL (0.25 mg/0.05 mL; TAC_sub), balanced salt solution (0.05mL was subconjunctivally injected in one eye of each rabbit and applied by eye drops in the other eye, control group), and Tacrolimus eye drops (5 mg/5 mL applied four times daily; TAC_drop). Digital photographs were obtained and the surface area of corneal neovascularization was measured 7 days after subconjunctival injections. Corneal specimens were analyzed histopathologically and were used to measure the concentration of VEGF, TNF‐α, IFN‐γ, IL‐1β, and MCP‐1 mRNA by RT‐PCR.ResultsIn digital photographs, the neovascularized area was decreased in all treatment groups (AVA_sub 0.58, TAC_sub 0.60, TAC_drop 0.68) compared with the control group (BSS 0.81). The histological examination showed markedly regressed new vessels in treatment groups, and the immunohistochemical staining revealed weakly stained with anti‐VEGF and anti‐F4/80 antibodies in the treatment groups. In semi‐quantitative RT‐PCR, the concentration of VEGF (AVA _sub 0.24, TAC_drop 0.18), TNF‐α (AVA_sub 0.19, TAC_sub 0.24, TAC_drop 0.15), and IL‐1ß (AVA_sub 0.19, TAC_sub 0.33, TAC_drop 0.18) mRNA were significantly lower in the treatment groups than in the control group (VEGF 0.47, TNF‐α 0.44, IL‐1β 0.87) (P < 0.05).ConclusionsTopical and subconjunctival tacrolimus application may be useful in reducing corneal neovascularization and have comparable effects to subconjunctival bevacizumab injection.