Preliminary study of the effect of FK506 nanospheric-suspension eye drops on rejection of penetrating keratoplasty.
ABSTRACT The aim of this study was to investigate the effect of a topical FK506 nanospheric suspension in a rat model of penetrating keratoplasty.
FK506 nanospheres were prepared by using a biodegradable poly (lactic-co-glycolic acid) copolymer (PLGA). Its distribution in the eye and blood after a single instillation was examined in rabbits. Sprague-Dawley (SD) rats received corneal heterografts and were topically treated with phosphate-buffered saline (PBS), PLGA, FK-506 0.01% (nanospheres), or dexamethasone 0.05% solutions twice a day for 28 days. Rejection index and graft-survival time were recorded and compared between the four groups. Three grafts were collected at different time points for immunohistochemical studies.
In the cornea, the FK-506 concentration reached its peak within 1 h of a single eye-drop instillation and then decreased by half (1667.85 +/- 611.87 ng/g) at 8 h. FK-506 cannot be detected in rabbit blood. There were significant differences in the graft-survival time between the FK-506 nanosphere group (15.09 +/- 4.81 days) and the other three groups [PBS (7.90 +/- 1.20, t = -4.594, P < 0.001), PLGA (8.44 +/- 0.88, t = - 4.074, P = 0.001) and dexamethasone (10.44 +/- 1.42, t = -2.790, P = 0.012)]. The rejected corneas in the FK506 nanosphere group showed significantly fewer CD4, CD8, CD68, CD79, vascular endothelial growth factor, ICAM, and tumor growth factor-beta(1)-positive cells than those in the other groups.
FK506 0.01% nanospheric-suspension eye drops delayed the occurrence of corneal allograft rejection and prolonged allograft survival time. The FK506 nanospheres may be valuable in suppressing corneal graft rejection.
Article: Corneal allograft rejection.British Journal of Ophthalmology 09/1994; 78(8):649-52. · 2.73 Impact Factor
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ABSTRACT: The immunosuppressive effect of FK 506 on penetrating keratoplasty in rats was evaluated following intramuscular and topical administration. Implanted corneal grafts were inspected weekly by clinical evaluation for 3 weeks. Cytotoxic T lymphocyte (CTL) activity was measured in the spleen on postoperative day 21, and the grafts were examined histologically. A dose of FK 506, 0.1 mg/kg given intramuscularly, only moderately suppressed CTL activity and the graft failed. In contrast, doses of either 0.024 mg/day topically or 0.3 mg/kg intramuscularly suppressed CTL activity and the grafts remained intact. Results suggest that FK 506 administered topically would be effective in preventing failure of human corneal grafts.Ophthalmologica 02/1996; 210(3):175-9. · 1.41 Impact Factor
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ABSTRACT: To evaluate frequency and risk factors of immunologic graft reactions after allogenic penetrating keratoplasty. Interventional comparative nonrandomized clinical trial. The setting took place in a university eye hospital. The retrospective study included 338 patients (338 eyes). The patients underwent penetrating keratoplasty performed by a single surgeon in the study period from 1989 to 1997. Follow-up period had to be longer than 12 months (mean +/- SD, 31.4 +/- 18.8 months). Frequency of immunologic graft reactions characterized by relatively few small monomorph whitish cells in the anterior chamber, almost no flare, and retrocorneal cellular precipitates. Immunologic graft reactions were detected in 46 patients (46/338 = 13.6%). Statistically significant risk factors for the development of graft reactions were loosening of sutures (P =.046), and preoperative and postoperative corneal vascularization (P =.04). Frequency of an immunologic graft reaction was statistically independent (P >.05) of the graft diameters used in the present study, age, and gender of the patients, HLA-typing, donor age, and preservation data of the donor material. Seventy-four percent (34/46) of all graft reactions were detected within the first 2.5 years after surgery. Thirteen percent (6/46) of all graft reactions were observed more than 4 years after keratoplasty. With intensive corticosteroid treatment, graft transparency could be regained in 44 (95.6%) of the 46 patients with an immunologic graft reaction. Most important risk factors for immunologic graft reactions occurring in approximately 14% of patients after allogenic penetrating keratoplasty are suture loosening and preoperative and postoperative corneal vascularization. Graft diameters as used in the present study, HLA-typing, age of the donor, and preservation data of the donor material may not play a major role. More than 10% of graft reaction episodes can occur more than 4 years postgrafting. With intensive corticosteroid treatment, graft transparency can be regained in the majority of patients after an immunologic graft reaction when detected early.American Journal of Ophthalmology 04/2002; 133(4):437-43. · 3.63 Impact Factor