Prolongation of corneal allograft survival using cyclosporine in a polylactide-co-glycolide polymer.
OBJECTIVE
To test for prolongation of corneal transplant survival with cyclosporine in a polymer placed in the anterior chamber of corneal allograft recipients.


METHODS
Wistar inbred rats with vascularized corneas were recipients of corneal allografts from Sprague-Dawley donor rats. Grafted rats were randomized into six groups: untreated control animals, cyclosporine-polymer anterior chamber recipients, cyclosporine-polymer subconjunctival recipients, cyclosporine-olive oil drop recipients, polymer-only anterior chamber recipients, and autografted Wistar rats. Grafts were examined by slit lamp every 3 days and the clinical condition scored. The cyclosporine concentration in the aqueous humor was assayed at 1, 2, and 4 weeks. At 2 and 4 weeks after transplantation, the eyes were collected for histopathologic evaluation of the grafts.


RESULTS
The median survival time of untreated corneal allografts was 8.2 +/- 1.48 days for grafts treated with topical cyclosporine, 8.5 +/- 1.50 days for polymer-only anterior chamber implants, 10.6 +/- 1.90 days for 1% cyclosporine drops, 11.4 +/- 2.50 days for grafts given subconjunctival cyclosporine-polymer, 17 +/- 3.05 days for grafts given cyclosporine-polymer implants in the anterior chamber, and more than 3 months in autografted rats. There was a statistically significant difference ( p < 0.05) between the survival time of the allografts in the animals treated with the cyclosporine-polymer in the anterior chamber compared with the other groups of graft recipients. Significantly higher concentrations of cyclosporine were found in the eyes given an anterior chamber implant of cyclosporine-polymer than in the other treatment groups or the untreated rats. The cyclosporine-polymer implants placed in the anterior chamber induced a transient inflammatory response in transplanted eyes.


CONCLUSIONS
Cyclosporine-polymer placed in the anterior chamber significantly prolongs corneal allograft survival in a high-risk corneal graft rejection. This intraocular delivery system may be a valuable adjunct for the suppression of immune graft rejection in high-risk recipients of corneal transplants.
Xie
L
L
Shandong Eye Institute and Hospital, 5 Yanerdao Road, Qingdao 266071, China. lixinxie@public.qd.sd.cn
Shi
W
W
Wang
Z
Z
Bei
J
J
Wang
S
S
D000818:Animals; D000867:Anterior Chamber / Q000187:drug effects; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D003315:Cornea / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D015948:Keratoplasty, Penetrating; D019344:Lactic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D011100:Polyglycolic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D014184:Transplantation, Homologous
D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D016572:Cyclosporine