title: Experimental efficacy of mycophenolate mofetil implant on high-risk corneal allograft rejection and its biocompatibility in the anterior chamber of rabbits.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao, PR China.
authors: Meng
authors: M
authors: Xin
authors: Ting
authors: T
authors: Wang
authors: Weiyun
authors: W
authors: Shi
authors: Xianggen
authors: X
authors: Wu
mesh_terms: D000818:Animals; D000867:Anterior Chamber; D016510:Corneal Neovascularization; D016039:Corneal Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004343:Drug Implants; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D015994:Incidence; D008297:Male; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology; D011817:Rabbits; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D004343:Drug Implants; D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid