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.