| Summary: | 碩士 === 國立交通大學 === 生物科技學系 === 105 === Age-related macular degeneration (AMD), is the leading cause of severe vision loss in aged individuals and the incidence of AMD is also increasing in the developed countries due to modern lifestyles. In this progressive disease, the degeneration of the retinal pigment epithelium (RPE) results in the death of photoreceptor, leading to a loss of central vision. The correlation between genomic mutation and AMD are poor, and the mechanism of AMD pathogenesis needs further elucidations. Besides, aging is the most determinative factor for AMD, it is widely accepted that build up of photo-inducible free radical overtime will lead to atrophy which the intermediate state of dry AMD. Furthermore, Musashi-1 (MSI-1), an RNA binding protein which is a neural stem cell marker and it is an expression in mature photoreceptor and RPE stem cells can be detected. It has been reported that MSI-1 knock-out mice results in degeneration of photoreceptor and lack of visual cycle had been reported. The aim of this study is to prove the hypothesis of proteopathy of AMD progression mediated by MSI-1 under oxidative stress condition in RPE cell line (ARPE-19). We found that MSI-1 protein translocated into the nucleus in cells treated with oxidative stress as compared to control cells that only expressed in the cytoplasm. Furthermore, we constructed MSI-1 domain swap and established stable cell expressing these construct. We found that wild-type and C-terminal Truncated Musashi-1 (MSI-1ΔC) cell showed the same phenotype in oxidative stress-treated cells and MSI-1ΔC results in higher apoptotic signals revealed by TUNEL assay. However expression profile of MSI-1 protein in control and treated cell with hydrogen peroxide are different. Taken together, our current result demonstrates that expression of MSI-1ΔC might deteriorate ARPE-19 cells when stimulated by free radicals. It is probable that MSI-1 is one of the critical factors that mediated AMD by proteopathy dependent pathway.
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