Xie Lixin, Shi Weiyun, Wang Zhiyu, Liu Zhaosheng
Shandong Eye Institute and Hospital, Qingdao 266071, China (Email:
Zhonghua Yan Ke Za Zhi. 2002 Jul;38(7):422-5.
To evaluate the efficacy and feasibility of cyclosporine A (CsA) drug delivery system (DDS) for prevention of high-risk corneal graft rejection in rats.
(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.
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.
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.
评估环孢素A（CsA）给药系统（DDS）预防大鼠高危角膜移植排斥反应的有效性和可行性。
（1）在60只Wistar大鼠（60只眼）的角膜基质中穿过8-0丝线诱导角膜血管化。（2）有角膜血管化的Wistar大鼠接受来自Sprague-Dawley大鼠的角膜移植以建立高危角膜移植模型。（3）40只动物模型（40只眼）分为4组：不接受治疗、1% CsA滴眼液、结膜下植入CsA DDS或前房植入CsA DDS。在1个月的随访期间，记录这些动物模型的存活时间（移植排斥反应发生时间），并定期检测房水中CsA浓度。（4）另外8只正常Wistar大鼠（16只眼）分为2组，结膜下或前房植入CsA DDS。在DDS植入后2周和4周对局部眼组织进行组织病理学检查。
51只Wistar大鼠（51只眼）成功诱导出角膜血管化，但另外9只大鼠因手术中或手术后出现并发症而失败。40只高危角膜移植动物模型（40只眼）均成功，呈现典型的排斥反应过程。4个试验组的平均存活时间分别为（8.20±1.48）天、（10.60±1.90）天、（11.40±2.50）天和（17.00±6.05）天。4个试验组房水中CsA的平均浓度分别为0μg/L、（47.90±3.48）μg/L、（56.50±6.24）μg/L、（121.70±16.79）μg/L。结膜下植入CsA DDS组术后1周、2周和4周房水中CsA的平均浓度分别为（58.96±3.66）μg/L、（59.74±6.50）μg/L、（50.66±4.13）μg/L，前房植入CsA DDS组在相应时间的平均浓度分别为（133.10±18.30）μg/L、（124.56±9.65）μg/L、（107.45±11.48）μg/L。CsA DDS植入后，局部眼组织出现慢性炎症，炎症逐渐减轻。
CsA DDS，尤其是前房植入的CsA DDS，可显著提高房水中CsA浓度并长时间维持高浓度，对预防高危角膜移植排斥反应作用强大且毒性极小。这是一种安全有效的CsA应用方法。
