期刊
INTERNATIONAL JOURNAL OF RETINA AND VITREOUS
卷 5, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s40942-019-0186-7
关键词
Sirolimus; LES; ARPE-19; Rapamycin; Uveitis
BackgroundTo evaluate the in vivo and in vitro toxicity of a new formulation of liposome-encapsulated sirolimus (LES).MethodsIn vitro experiments were done using ARPE-19 and HRP cells. An MTT assay was used to determine cell metabolic activity and a TUNEL assay for detecting DNA fragmentation. In vivo experiments were conducted on New Zealand albino rabbits that received intravitreal injections of empty liposomes (EL) or different concentrations of LES. Histopathological and immunohistochemical analyses were performed on the rabbit's eyes following injection.ResultsEighteen eyes of nine rabbits were used. MTT assay cell viability was 95.04% in group 1 (12.5 mu L/mL LES). 92.95% in group 2 (25 mu L/mL LES), 91.59% in group 3 (50 mu L/mL LES), 98.09% in group 4 (12.5 mu L/mL EL), 95.20% on group 5 (50 mu L/mL EL), 98.53% in group 6 (50 mu L/mL EL), and 2.84% on group 8 (50 mu L/mL DMSO). There was no statistically significant difference among groups 1 to 7 in cell viability (p=1.0), but the comparison of all groups with group 8 was significant (p<0.0001). The TUNEL assay comparing two groups was not statistically significant from groups 1 to 7 (p=1.0). The difference between groups 1 to 7 and group 8 (p<0.0001) was significant. Histopathological changes were not found in any group. No activation of Muller cells was detected.ConclusionA novel formulation of LES delivered intravitreally did not cause in vitro toxicity, as evaluated by MTT and TUNEL assays, nor in vivo toxicity as evaluated by histopathology and immunohistochemistry in rabbit eyes.
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