Experimental study on the effect of cyclosporine A drug delivery system implanted in anterior chamber on high-risk corneal graft rejection.
OBJECTIVE
To evaluate the efficacy and feasibility of cyclosporine A (CsA) drug delivery system (DDS) for prevention of high-risk corneal graft rejection in rats.


METHODS
(1) Corneal vascularization was induced in 60 Wistar rats (60 eyes) by passing 8-0 silk suture in corneal stroma. (2) Wistar rats with corneal vascularization received corneal grafts from Sprague-Dawley rats to develop the high-risk keratoplasty models. (3) Forty animal models (40 eyes) were divided into 4 groups: receiving no therapy, 1% CsA eye drop, CsA DDS implanted subconjunctively, or CsA DDS implanted in anterior chamber. During the 1-month follow-up, survival times (the occurrence time of graft rejection) of these animal models were recorded, and CsA concentration in aqueous humor was regularly detected. (4) Other 8 normal Wistar rats (16 eyes) were divided into 2 groups with CsA DDS implanted subconjunctively or in anterior chamber. Histopathological examination on local ocular tissues was performed at 2 and 4 weeks after DDS implantation.


RESULTS
Corneal vascularization was successfully induced in 51 Wistar rats (51 eyes), but failed in the other 9 rats because of complications in or after operation. 40 high-risk keratoplasty animal models (40 eyes) were all successful which exhibited typical rejection processes. The mean survival time of 4 trial groups was (8.20 +/- 1.48) days, (10.60 +/- 1.90) days, (11.40 +/- 2.50) days and (17.00 +/- 6.05) days respectively. The mean CsA concentration in aqueous humor of 4 trial groups was 0 micro g/L, (47.90 +/- 3.48) micro g/L, (56.50 +/- 6.24) micro g/L, (121.70 +/- 16.79) micro g/L respectively. The mean CsA concentration in aqueous humor of CsA DDS subconjunctively implanted group was (58.96 +/- 3.66) micro g/L, (59.74 +/- 6.50) micro g/L, (50.66 +/- 4.13) micro g/L at 1, 2 and 4 weeks postoperatively, and the mean CsA concentration of CsA DDS intrachamberly implanted group was (133.10 +/- 18.30) micro g/L, (124.56 +/- 9.65) micro g/L, (107.45 +/- 11.48) micro g/L at the corresponding time. After CsA DDS implantation, chronic inflammation occurred in local ocular tissues, and the inflammation reduced gradually.


CONCLUSIONS
The CsA DDS, especially CsA DDS implanted in anterior chamber, can significantly improve CsA concentration in aqueous humor and maintain a high concentration for a long period of time, which has strong effects on prevention of high-risk corneal graft rejection with only little toxicity. It is a safe and effective method for CsA application.
Xie
Lixin
L
Shandong Eye Institute and Hospital, Qingdao 266071, China (Email: lixinxie@public.qd.sd.cn)
Shi
Weiyun
W
Wang
Zhiyu
Z
Liu
Zhaosheng
Z
D000818:Animals; D000867:Anterior Chamber; D016039:Corneal Transplantation; D016572:Cyclosporine / Q000008:administration & dosage; D016503:Drug Delivery Systems; D006084:Graft Rejection / Q000517:prevention & control; D006085:Graft Survival; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D007166:Immunosuppressive Agents; D016572:Cyclosporine