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Restoration of visual function in advanced disease after transplantation of purified human pluripotent stem cell-derived cone photoreceptors.
Ribeiro, Joana; Procyk, Christopher A; West, Emma L; O'Hara-Wright, Michelle; Martins, Monica F; Khorasani, Majid Moshtagh; Hare, Aura; Basche, Mark; Fernando, Milan; Goh, Debbie; Jumbo, Neeraj; Rizzi, Matteo; Powell, Kate; Tariq, Menahil; Michaelides, Michel; Bainbridge, James W B; Smith, Alexander J; Pearson, Rachael A; Gonzalez-Cordero, Anai; Ali, Robin R.
Afiliación
  • Ribeiro J; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Procyk CA; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • West EL; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • O'Hara-Wright M; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Martins MF; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Khorasani MM; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Hare A; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Basche M; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Fernando M; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Goh D; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Jumbo N; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Rizzi M; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Powell K; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Tariq M; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Michaelides M; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Bainbridge JWB; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Smith AJ; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Pearson RA; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Gonzalez-Cordero A; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK.
  • Ali RR; UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; Kellogg Eye Centre, University of Michigan, 1000 Wall St., Ann Arbor, MI 48105, USA. Electronic address: robin.ali@kcl.ac.uk.
Cell Rep ; 35(3): 109022, 2021 04 20.
Article en En | MEDLINE | ID: mdl-33882303
Age-related macular degeneration and other macular diseases result in the loss of light-sensing cone photoreceptors, causing irreversible sight impairment. Photoreceptor replacement may restore vision by transplanting healthy cells, which must form new synaptic connections with the recipient retina. Despite recent advances, convincing evidence of functional connectivity arising from transplanted human cone photoreceptors in advanced retinal degeneration is lacking. Here, we show restoration of visual function after transplantation of purified human pluripotent stem cell-derived cones into a mouse model of advanced degeneration. Transplanted human cones elaborate nascent outer segments and make putative synapses with recipient murine bipolar cells (BCs), which themselves undergo significant remodeling. Electrophysiological and behavioral assessments demonstrate restoration of surprisingly complex light-evoked retinal ganglion cell responses and improved light-evoked behaviors in treated animals. Stringent controls exclude alternative explanations, including material transfer and neuroprotection. These data provide crucial validation for photoreceptor replacement therapy and for the potential to rescue cone-mediated vision.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Células Fotorreceptoras Retinianas Conos / Recuperación de la Función / Células Madre Pluripotentes Inducidas / Degeneración Macular Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Organoides / Células Fotorreceptoras Retinianas Conos / Recuperación de la Función / Células Madre Pluripotentes Inducidas / Degeneración Macular Idioma: En Revista: Cell Rep Año: 2021 Tipo del documento: Article Pais de publicación: Estados Unidos