Your browser doesn't support javascript.
loading
Investigation of PTC124-mediated translational readthrough in a retinal organoid model of AIPL1-associated Leber congenital amaurosis.
Leung, Amy; Sacristan-Reviriego, Almudena; Perdigão, Pedro R L; Sai, Hali; Georgiou, Michalis; Kalitzeos, Angelos; Carr, Amanda-Jayne F; Coffey, Peter J; Michaelides, Michel; Bainbridge, James; Cheetham, Michael E; van der Spuy, Jacqueline.
Afiliación
  • Leung A; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • Sacristan-Reviriego A; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • Perdigão PRL; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • Sai H; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • Georgiou M; UCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
  • Kalitzeos A; UCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
  • Carr AF; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • Coffey PJ; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • Michaelides M; UCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
  • Bainbridge J; UCL Institute of Ophthalmology, London EC1V 9EL, UK; Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK.
  • Cheetham ME; UCL Institute of Ophthalmology, London EC1V 9EL, UK.
  • van der Spuy J; UCL Institute of Ophthalmology, London EC1V 9EL, UK. Electronic address: j.spuy@ucl.ac.uk.
Stem Cell Reports ; 17(10): 2187-2202, 2022 10 11.
Article en En | MEDLINE | ID: mdl-36084639
ABSTRACT
Leber congenital amaurosis type 4 (LCA4), caused by AIPL1 mutations, is characterized by severe sight impairment in infancy and rapidly progressing degeneration of photoreceptor cells. We generated retinal organoids using induced pluripotent stem cells (iPSCs) from renal epithelial cells obtained from four children with AIPL1 nonsense mutations. iPSC-derived photoreceptors exhibited the molecular hallmarks of LCA4, including undetectable AIPL1 and rod cyclic guanosine monophosphate (cGMP) phosphodiesterase (PDE6) compared with control or CRISPR-corrected organoids. Increased levels of cGMP were detected. The translational readthrough-inducing drug (TRID) PTC124 was investigated as a potential therapeutic agent. LCA4 retinal organoids exhibited low levels of rescue of full-length AIPL1. However, this was insufficient to fully restore PDE6 in photoreceptors and reduce cGMP. LCA4 retinal organoids are a valuable platform for in vitro investigation of novel therapeutic agents.
Asunto(s)
Palabras clave
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Amaurosis Congénita de Leber Tipo de estudio: Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Stem Cell Reports Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Amaurosis Congénita de Leber Tipo de estudio: Risk_factors_studies Límite: Child / Humans Idioma: En Revista: Stem Cell Reports Año: 2022 Tipo del documento: Article País de afiliación: Reino Unido