Year: 2018
Type: article
Abstract: mutation and successfully established an in vitro model of BCD, i.e., BCD patient-specific iPSC-RPE cells. In this model, RPE cells showed degenerative changes of vacuolated cytoplasm similar to those in postmortem specimens from patients with BCD. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of autophagy flux, followed by cell death. Lipidomic analyses revealed the accumulation of glucosylceramide and free cholesterol in BCD-affected cells. Notably, we found that reducing free cholesterol by cyclodextrins or δ-tocopherol in RPE cells rescued BCD phenotypes, whereas glucosylceramide reduction did not affect the BCD phenotype. Our data provide evidence that reducing intracellular free cholesterol may have therapeutic efficacy in patients with BCD.
Institutions: Kyoto University, Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Center for iPS Cell Research and Application, Kyoto University, RIKEN Center for Integrative Medical Sciences, Yokohama City University, Niigata University of Pharmacy and Medical and Life Sciences, Keio University
Language: English
Subfield: Genetics (clinical)
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Awards: Investigation of the cell protective abilities of branched chain amino acids in mouse models of retinal neurodegenerative diseases, Elucidation of disease pathogenesis associated with dysregulated lipid metabolism and their potential therapeutic applications, Development of new treatment for age-related macular degeneration, Histopathological changes and their autoimmune mechanisms in chorioretinal diseases, G4822450984, G5279953610, Development of treatment for Bietti crystalline dystrophy, Pathological elucidation in induced Pluripotent Stem Cell-Derived Retinal Pigment Epithelial Cells established from Patient with Retinitis Pigmentosa Carrying novel gene abnormality, Development of neuroprotective treatments for ischemic eye diseases., G8396234061, G8596147609
OpenAlex ID: W2789976847