Activation of autophagy reverses progressive and deleterious protein aggregation in PRPF31 patient-induced pluripotent stem cell-derived retinal pigment epithelium cells.
Maria GeorgiouChunbo YangRobert AtkinsonKuan-Ting PanAdriana BuskinMarina Moya MolinaJoseph CollinJumana Al-AamaFranziska GoertlerSebastian E J LudwigTracey DaveyReinhard LührmannSushma Nagaraja-GrellscheidColin A JohnsonRobin AliLyle ArmstrongViktor KorolchukHenning UrlaubSina Mozaffari-JovinMajlinda LakoPublished in: Clinical and translational medicine (2022)
Our data demonstrate that it is the progressive aggregate accumulation that overburdens the waste disposal machinery rather than direct PRPF31-initiated mis-splicing, and thus relieving the RPE cells from insoluble cytoplasmic aggregates presents a novel therapeutic strategy that can be combined with gene therapy studies to fully restore RPE and retinal cell function in PRPF31-adRP patients.
Keyphrases
- gene therapy
- end stage renal disease
- multiple sclerosis
- induced apoptosis
- ejection fraction
- newly diagnosed
- chronic kidney disease
- endoplasmic reticulum stress
- cell death
- peritoneal dialysis
- oxidative stress
- optical coherence tomography
- prognostic factors
- high glucose
- cell cycle arrest
- electronic health record
- diabetic rats
- municipal solid waste
- big data
- small molecule
- protein protein
- stress induced
- sewage sludge