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Ana Paula Canto, Yaohong Tan, Mohamed Abou Shousha, Carolina Betancurt, Jose Echegaray-Mendez, Victor L. Perez; The Effect of Low-dose Rapamycin on Prolonging High-Risk Corneal Allograft Survival in a Mouse Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):374.
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Immune rejection is a cause of corneal graft failure. Rapamycin (RAPA) is an immunosuppressant that inhibits activation and proliferation of T-cell and the production of interleukin-2. We aimed to study the effect of a low-dose RAPA systemic treatment, started previously or on the day of the corneal transplant, on prolonging high-risk corneal allograft survival in a mouse model of penetrating keratoplasty.
Orthotopic corneal allotransplants were performed in high-risk (vascularized) C57BL/6 recipients. Balb/c served as donors. Corneal sutures were removed at post-operative day 7 (POD7). Grafts were evaluated twice a week, beginning on POD7 using a clinical score for corneal clarity. Grafts were considered rejected if a score of 3 or more was observed for two consecutive days without clearance. Control group (n=10) received the graft and remained untreated. Post-treated group (n=6) received the graft and was treated with daily intraperitoneal (IP) injections of RAPA (0.5mg/kg/day) starting on the day of the surgery and continued daily until rejection occurred. Pre-treated group (n=7) was pre-treated with daily RAPA IP injections (0.5mg/kg/day) for 7 days previous surgery and for the consecutive days until rejection occurred.
Corneal allografts in high-risk control untreated recipients were rejected at 14.70±1.49 days with a statistically significant difference from the RAPA treated group (p<0.01). The post-treated group rejected their grafts at 33.50±12.49 days. The pre-treated group rejected their grafts at 27.57±7.63 days. There was no significantly prolonged corneal graft survival comparing the pre-treated and post-treated RAPA groups (p>0.05).
Even though, systemic rapamycin low-dose therapy treatment started previous surgery does not significantly prolonged corneal high-risk allograft survival; it did significantly prolonged high-risk allograft survival in a mouse model of penetrating keratoplasty and can be used to prevent rejection of high-risk corneal allografts.
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