State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, PR China.
J Ocul Pharmacol Ther. 2012 Dec;28(6):609-17. doi: 10.1089/jop.2012.0065. Epub 2012 Jul 30.
The aim of this study was to investigate the immunosuppressive activity of a mycophenolate mofetil (MMF) intraocular-implantable drug delivery system (IDDS) in a rabbit model of high-risk penetrating keratoplasty and to determine the biocompatibility of such a device when implanted in the anterior chamber.
Corneal vascularization was induced in New Zealand white rabbits by passing 5-0 silk sutures through the corneal stroma in each quadrant. The corneal neovascularized rabbits received a unilateral 7-mm-diameter central-penetrating keratoplasty. New Zealand white rabbits were used as donors and were divided into 4 treatment groups: the control group, which received no therapy; the 1% MMF eye drop group; the 1.0 mg cyclosporin A (CsA)-IDDS-implanted group; and the 1.0 mg MMF-IDDS-implanted group. Animals were followed up for 150 days, which involved examination of the corneal allografts (opacity, edema, and neovascularization) by slit-lamp biomicroscopy. The survival time of corneal allografts of these animal models was recorded in 4 groups. Histopathologic studies were carried out on the procured specimens of corneal allografts. The biocompatibility of MMF-IDDS in the anterior chamber in rabbits was also investigated.
The mean survival time of corneal allografts in the control and MMF eye drop groups was 18.7±3.0 and 37.5±6.2 days, respectively (P=0.005). Allografts from the CsA-IDDS-implanted group were transparent, except 1 allograft, which showed immune rejection after 130 days. Allografts from the MMF-IDDS-implanted group were transparent throughout the entire observation period. The incidence of allograft rejection was 100% in the control and MMF eye drop groups, respectively. The rejected allografts were much more edematous and more heavily infiltrated with leukocytes than the nonrejected allografts. MMF-IDDS was tolerated well in the anterior chamber, even with 3 MMF-IDDS implanted in the anterior chamber at 1 time.
MMF-IDDS was able to prolong high-risk allograft survival time and significantly inhibited corneal immune rejection in the rabbit model of penetrating keratoplasty. The device could safely be implanted in the anterior chamber without adverse effects.
本研究旨在探讨霉酚酸酯（MMF）眼内植入型药物递送系统（IDDS）在高风险穿透性角膜移植兔模型中的免疫抑制活性，并确定该装置在前房内植入时的生物相容性。
通过在每个象限的角膜基质中穿过 5-0 丝线，诱导新西兰白兔角膜血管化。角膜新生血管化的兔子接受单侧 7mm 直径中央穿透性角膜移植。新西兰白兔被用作供体，并分为 4 个治疗组：对照组，未接受治疗；1%MMF 滴眼液组；1.0mg 环孢素 A（CsA）-IDDS 植入组；和 1.0mg MMF-IDDS 植入组。动物随访 150 天，通过裂隙灯生物显微镜检查角膜同种异体移植物（混浊、水肿和新生血管化）。记录这 4 组动物模型角膜同种异体移植物的存活时间。对获取的角膜同种异体移植物标本进行组织病理学研究。还研究了 MMF-IDDS 在兔前房内的生物相容性。
对照组和 MMF 滴眼液组角膜同种异体移植物的平均存活时间分别为 18.7±3.0 和 37.5±6.2 天（P=0.005）。CsA-IDDS 植入组的同种异体移植物均透明，除 1 例同种异体移植物在 130 天后发生免疫排斥反应。MMF-IDDS 植入组的同种异体移植物在整个观察期内均透明。对照组和 MMF 滴眼液组的同种异体移植物排斥发生率分别为 100%。排斥的同种异体移植物比未排斥的同种异体移植物水肿更严重，白细胞浸润更多。即使在 1 次前房内植入 3 个 MMF-IDDS，MMF-IDDS 在前房内也能很好耐受。
MMF-IDDS 能够延长高危同种异体移植物的存活时间，并显著抑制穿透性角膜移植兔模型中的角膜免疫排斥反应。该装置可以安全地植入前房，无不良反应。
