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I. Berra, G. Zapata, V. Reviglio, C. Echeverria, A. Berra; Clinical Immunosuppressive Evaluation of Sirolimus and Cyclosporine Using Topic Administration in a Murine Model of Stromal Herpetic Keratitis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5127.
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to evaluate and to compare the clinical findings of immunosuppressive effects of sirolimus and cyclosporine in topic administration in an experimental model of Herpetic Stromal Keratitis (HSK) in mouse.
right cornea of anaesthetized adult Balb/c mice were inoculated with 2.5 × 104 PFU of HSV-1 (group control). Other animals were also treated with aciclovir 3 % (ACICLOVIR) or dexamethasone 0.1% (DEX) or sirolimus 0.5% (SIRO) and cyclosporine 0.5 % (CICLO), the immunosuppressive drugs were administered topically in the infected cornea, three times a day. The treatment started one day after inoculation (a.i.) until day seven. The corneal neovascularization and opacity (signs of HSK) were clinically registered at day 7 and 14 a.i.
in order to measure the severity of corneal neovascularization and opacity were clinically scored. The results were at day 7 a.i. in group SIRO (1.8 ± 0.3; 2.5 ± 0.6), group CICLO (1.6 ± 0.5; 1.5 ± 0.5), group DEX (1.9 ± 0.5; 1.9 ± 0.6), group control (0.4 ± 0.2; 0.8 ± 0.4) y group aciclovir (0.5 ± 0.3; 0 ± 0). The severity of disease at 7 day a.i. in mice treated with dexamethasone, sirolimus y cyclosporin increased considerably respect to control and aciclovir treated animals were significantly (p<0.05) (non-parametric Mann-Whitney test). The clinical following of animals did not present significantly differences between groups at day 14 a.i.. SIRO (4 ± 0; 4 ± 0), CICLO (3.25 ± 0.49; 2.87 ± 0.48) , DEX (3.56 ± 0.18; 3.89 ± 0.11) and control (3.89 ± 0.11; 3.89 ± 0.11). However, we observed significantly difference with aciclovir group (0.89 ± 0.59; 0.89 ± 0.59).
The systemic use of immunosuppressive drugs can lead to serious adverse side effects that can be avoided using the topical formulation. Based on the obtanined results comparing sirolimus and cyclosporin with dexamethasone which were no significant at day 7 and 14 a.i. but with significant difference with control and aciclovir group at day 7. These data suggest that the immunosuppression of the ocular surface leads to an early development of the HSK. Conclusively, the present sirolimus and cyclosporine eye drops might be promising therapeutic tools for the immunomodulatory treatment of ocular surface disorders
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