Protective role of anti-TLR2 monoclonal antibody to corneal graft survival after allograft corneal transplantation in rats / 中华实验眼科杂志

ABSTRACT

Background The effects of Toll-like receptor 2 (TLR2) in grafting-related immune diseases have attracted more and more attention.Blocking TLR2 signal pathway can extend the survival time of heart and kidney grafts.However, the effects of anti-TLR2 monoclonal antibody on corneal graft have not been confirmed.Objective This study was to investigate the influence of anti-TLR2 monoclonal antibody on corneal graft survival in the rats received penetrating keratoplasty (PKP).Methods Allograft corneal transplantation was performed on the right eyes of 24 SPF female Wistar rats to establish PKP models,with 12 SD rats as donors.The model eyes were randomized into the TLR2 monoclonal antibody group and the model group.Anti-TLR2 monoclonal antibody of 15 μg/30 μl was subconjunctivally injected on day 0,2,4,6 and 8 following the modeling in the TLR2 monoclonal antibody group,and equal amount of normal saline was injected in the same way in the model group.The edema,transparency and neovascularization were observed under the slit lamp microscope after surgery, and rejection index (RI) was scored based on the criteria of Holland.Corneal tissue sections of the rats were prepared for the histopathological examination on day 9 and 15 after operation.The research protocol was approved by the Southern Medical University Ethics Committee.Results Mild corneal edema was found in the two groups 1-4 days after operation.A lot of new blood vessels, edema and opacification of corneas were seen in the model group 9-14 days after operation,but in the TLR2 monoclonal antibody group,corneal opacification was found 15 days after operation.The RI scores were significantly higher in the model group than those in the TLR2 monoclonal antibody group 5,9,15 days after operation (t=4.183,4.954,13.506;all at P＜0.05).The survival time in the TLR2 monoclonal antibody group was 15.5 days,with the 95％ confidence interval (CI) 14.9-16.1;while that in the model group was 9.5 days,with the 95％ CI 8.7-10.3, showing a significant difference between the two groups (Z =12.728,P =0.001).The corneal histopathological examination revealed that corneal stromal edema,infiltration of inflammatory cells and vascular lumen were more prominent 9 and 15 days after operation in the model group than those in the TLR2 monoclonal antibody group.Conclusions Anti-TLR2 monoclonal antibody can inhibit inflammatory response after allograft corneal transplantation and therefore extend the survival time of graft in rats.