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목적 : To investigate protective effect of idebenone on ethambutol induced toxicity in R28 retinal precursor cell line and mice.
방법 : Cell viability assay was measured by ATP content and cell counting kit-8. Reactive osygen species (ROS), superoxide, mitochondrial ROS were also measured. Bcl2, Apoptosis inducing factor (AIF), caspase-3 were measured by confocal microscope. For in vivo assay, ethambutol was administered intraperitoneally in C57BL/6N male mice for 6 weeks. Optical coherence tomography, fundus photo, electroretinogram (ERG), optomotor test were done after 6 weeks ethambutol treatment.
결과 : In R28 cell lines, EMB-induced cytoplasmic vacuolization was not prevented by idebenone treatment. However, cell viability was increased with pre-treatment of idebenone. Idebenone reduced mitochondrial ROS, AIF translocation and lysosomal activation. In vivo model, idebenone co-treated mice showed preserved ERG, optomotor function compared to only EMB-treated mice. Idebenone also protect retinal ganglion cells, reduction in retinal thickness and gliosis.
결론 : Idebenone protect ethambutol induced toxicity with modest effect in R28 cell line and mice model. Idebenone reduces mitochondrial ROS, and it also suppress lysosomal-autophagosome activation via altering AIF translocation.
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