title: Modeling retinal degeneration using patient-specific induced pluripotent stem cells.
abstract: Retinitis pigmentosa (RP) is the most common inherited human eye disease resulting in night blindness and visual defects. It is well known that the disease is caused by rod photoreceptor degeneration; however, it remains incurable, due to the unavailability of disease-specific human photoreceptor cells for use in mechanistic studies and drug screening. We obtained fibroblast cells from five RP patients with distinct mutations in the RP1, RP9, PRPH2 or RHO gene, and generated patient-specific induced pluripotent stem (iPS) cells by ectopic expression of four key reprogramming factors. We differentiated the iPS cells into rod photoreceptor cells, which had been lost in the patients, and found that they exhibited suitable immunocytochemical features and electrophysiological properties. Interestingly, the number of the patient-derived rod cells with distinct mutations decreased in vitro; cells derived from patients with a specific mutation expressed markers for oxidation or endoplasmic reticulum stress, and exhibited different responses to vitamin E than had been observed in clinical trials. Overall, patient-derived rod cells recapitulated the disease phenotype and expressed markers of cellular stresses. Our results demonstrate that the use of patient-derived iPS cells will help to elucidate the pathogenic mechanisms caused by genetic mutations in RP.
authors.affiliation: Laboratory for Retinal Regeneration, RIKEN Center for Developmental Biology, Kobe, Japan.
authors.forename: Zi-Bing
authors.initials: ZB
authors.lastname: Jin
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okamoto
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Osakada
authors.forename: Kohei
authors.initials: K
authors.lastname: Homma
authors.forename: Juthaporn
authors.initials: J
authors.lastname: Assawachananont
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Hirami
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iwata
authors.forename: Masayo
authors.initials: M
authors.lastname: Takahashi
mesh_terms: D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005260:Female; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008954:Models, Biological; D009154:Mutation; D012162:Retinal Degeneration / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000473:pathology
chemical_list: D000975:Antioxidants