Shi Wei-yun, Liu Ting, Xie Li-xin, Wang Shen-guo
Shandong Provincial Key Lab of Ophthalmology, Shandong Eye Institute, Qingdao 266071, China.
Zhonghua Yan Ke Za Zhi. 2006 Apr;42(4):299-304.
To study the effects of a biodegradable FK506 drug delivery system (DDS) on the inhibition of corneal rejection, to measure the concentration of FK506 in the aqueous humor and to study the relationship between intraocular concentration of FK506 and its immunosuppressive effects on corneal rejection.
Corneal neo-vascularization was induced by 5 - 0 silk sutures in 68 New Zealand rabbits to establish a high risk corneal transplantation model. A unilateral 7 mm diameter central penetrating corneal transplantation was performed with 7.5 mm diameter grafts from health New Zealand rabbit donors. Grafted rabbits were randomized into five groups as follows: Group A: untreated control animals; Group B: DDS anterior chamber recipients without drug; Group C: 1 mg cyclosporine DDS anterior chamber recipients; Group D: 0.1% FK506-olive oil drop recipients; Group E: 0.5 mg FK506 DDS anterior chamber recipients. Grafts were examined with a slit lamp every other day and clinical conditions were scored for up to 28 weeks. The aqueous humor and cornea of Group D and Group E were collected, and the concentration of FK506 was determined. The expression of cytokines IL-2R alpha, MCP-1, Fas and FasL mRNA was detected with in situ hybridization method.
The median survival time was (17.9 +/- 4.7) d in Group A (untreated corneal allograft), (20.0 +/- 3.7) d in Group B, (56.3 +/- 8.8) d in Group C, (78.1 +/- 7.2) d in Group D, and over 180 d in Group E. Statistically significant difference (F = 926.37, P = 0.0000) in the survival time of allograft has been found between Group E and other groups. The concentration of FK506 in aqueous humor was (15.7 +/- 2.6) ng/ml in Group E at one week and remained stable for at least 24 weeks, much higher than that in Group D (<0.3 ng/ml). The concentration of FK506 in cornea was also higher in Group E than that in Group D. The expression of cytokines IL-2R alpha and MCP-1 mRNA was detected, but the expression of Fas and FasL mRNA was not detected in Group A.
FK506 DDS implanted in the anterior chamber can significantly prolong corneal allograft survival in high-risk corneal graft rejection model. This intraocular DDS may be a valuable adjunct for the suppression of immune graft rejection in high-risk corneal transplants.
研究可生物降解的FK506药物递送系统（DDS）对角膜移植排斥反应的抑制作用，测量房水中FK506的浓度，并研究FK506眼内浓度与其对角膜移植排斥反应的免疫抑制作用之间的关系。
用5-0丝线诱导68只新西兰兔角膜新生血管形成，建立高风险角膜移植模型。用来自健康新西兰兔供体的直径7.5mm的移植物进行单侧直径7mm的中央穿透性角膜移植。将移植后的兔子随机分为五组：A组：未治疗的对照动物；B组：接受无药物的DDS前房植入物的动物；C组：接受1mg环孢素DDS前房植入物的动物；D组：接受0.1%FK506-橄榄油滴剂的动物；E组：接受0.5mg FK506 DDS前房植入物的动物。每隔一天用裂隙灯检查移植物，并对临床情况进行评分，最长持续28周。收集D组和E组的房水和角膜，测定FK506的浓度。用原位杂交法检测细胞因子IL-2Rα、MCP-1、Fas和FasL mRNA的表达。
A组（未治疗的角膜同种异体移植）的中位生存时间为（17.9±4.7）天，B组为（20.0±3.7）天，C组为（56.3±8.8）天，D组为（78.1±7.2）天，E组超过180天。E组与其他组之间在同种异体移植物生存时间上存在统计学显著差异（F = 926.37，P = 0.0000）。E组在一周时房水中FK506的浓度为（15.7±2.6）ng/ml，并至少在24周内保持稳定，远高于D组（<0.3 ng/ml）。E组角膜中FK506的浓度也高于D组。检测到细胞因子IL-2Rα和MCP-1 mRNA的表达，但在A组中未检测到Fas和FasL mRNA的表达。
植入前房的FK506 DDS可显著延长高风险角膜移植排斥模型中角膜同种异体移植物的存活时间。这种眼内DDS可能是抑制高风险角膜移植免疫排斥反应的一种有价值的辅助手段。
