Interleukin-1 receptor antagonist eye drops promoting high-risk corneal allografts survival in rats.
BACKGROUND
Immune rejection is the main reason of grafts failure after corneal transplantation. This study was to determine whether interleukin-1 receptor antagonist (IL-1ra) eye drops could prolong corneal allografts survival in high-risk corneal orthotopic allotransplantation in rat model and to study the effect of IL-1ra on the expression of CD1-positive cells in the grafts.


METHODS
For all experiments, the Sprague-Dawley (SD) rats' corneas were transplanted into Wistar rats' eyes. High-risk transplants included those that had been sutured into Wistar recipient beds with corneal neovascularization induced by placement of three interrupted sutures in the host cornea 7 days earlier. All the animals were divided, in a masked fashion, into three treatment groups and one control group. Each treatment group received IL-1ra eye drops of different concentrations (1 mg/ml, 3 mg/ml, or 5 mg/ml, respectively) four times a day for 30 days. The control group received 0.9% normal saline (NS) eye drops in the same way as the treatment groups. All allografts were evaluated for signs of rejection from the first day after surgery. Ten days later, corneal specimens were processed to examine the expression of CD1-positive cells and histopathological changes.


RESULTS
The survival time of the transplants was 5.80 +/- 0.79, 5.89 +/- 1.05, 6.78 +/- 0.83, and 9.00 +/- 2.36 days respectively in the control or three treatment groups. Compared with the control group, 1 mg/ml IL-1ra eye drop did not prolong the survival time of the allografts (t = 0.210, P > 0.05). However, 3 mg/ml and 5 mg/ml IL-1ra eye drop did prolong the survival time of the grafts (t >or= 2.627, P < 0.05), with the latter showing more obvious effect. Immunohistochemical examinations showed a significant decrease in inflammatory cell and CD1-positive cell infiltration in IL-1ra treated groups compared with the control group.


CONCLUSIONS
IL-1ra can promote corneal allograft survival in a dose-dependant manner by reducing the infiltration of CD1-positive cells in high-risk corneal transplantation.
Jie
Ying
Y
Institute of Ophthalmology, Tongren Eye Centre, Tongren Hospital, Capital University of Medical Sciences, Beijing 100730, China.
Zhang
Wen-hua
WH
Pan
Zhi-qiang
ZQ
Wu
Yu-ying
YY
Wang
Ying
Y
D000818:Animals; D018949:Antigens, CD1 / Q000032:analysis; D003315:Cornea / Q000473:pathology; D016039:Corneal Transplantation; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D007150:Immunohistochemistry; D053590:Interleukin 1 Receptor Antagonist Protein; D009883:Ophthalmic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012306:Risk; D012795:Sialoglycoproteins / Q000008:administration & dosage*; D014184:Transplantation, Homologous
D018949:Antigens, CD1; D053590:Interleukin 1 Receptor Antagonist Protein; D009883:Ophthalmic Solutions; D012795:Sialoglycoproteins