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W. Shi, H. Gao, L. Xie; Sustained Rapamycin Drug Delivery System for Prevention of High Risk Corneal Allograft Rejection and Neovascularization in Rabbits . Invest. Ophthalmol. Vis. Sci. 2005;46(13):5047.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To evaluate the immunosuppressive effect and mechanism of action of rapamycin drug delivery system (RAPA DDS) in prolonging allograft survival and inhibiting corneal neovascularization in rabbits with high risk orthotopic penetrating keratoplasty. Methods: Forty New Zealand white rabbits (40 eyes) with high risk penetrating keratoplasty were divided into control group, 0.5 mg polyclatide–coglycolide–co–caprolactone (PGLC) implanted in anterior chamber group, 1% RAPA drops group and RAPA DDS (0.5 mg RAPA incorporated with 0.5 mg PGLC) implanted in anterior chamber group. The allograft survival and neovascularization were observed. RAPA concentration in aqueous humor was measured with high–performance liquid chromatography–mass spectrometry. The expression of IL–2R, MCP–1 and Fas/FasL in rejected corneal tissue was detected by in situ hybridization. The secretion of TNF–α and VEGF was detected using immunohistochemical techniques. Results: The mean survival time of corneal grafts was 16.5, 16.0, 47.1 and 87.6 days respectively in the control group, PGLC group, RAPA drops group and RAPA DDS group (P=0.000). The corneal neovascularization was well inhibited in the RAPA treated animals. The aqueous humor RAPA concentration was 10.7, 12.0, 9.2 and 7.0 ng/ml respectively at 2, 4, 8 and 12 weeks in the RAPA DDS group, but not detected in the RAPA drops group. IL–2R, MCP–1, TNF–α and VEGF were overexpressed in the rejected corneal tissue in the control group and PGLC group, but undetectable in the RAPA treated groups. Fas and FasL were negative in all corneal tissue. Conclusions: RAPA DDS can play an important role in prolonging allograft survival and preventing corneal neovascularization by inhibiting the expression of IL–2R, MCP–1, TNF–α and VEGF in high risk keratoplasty model. RAPA DDS appears to be a novel therapeutic approach for corneal transplantation.
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