UCL  IRIS
Institutional Research Information Service
UCL Logo
Please report any queries concerning the funding data grouped in the sections named "Externally Awarded" or "Internally Disbursed" (shown on the profile page) to your Research Finance Administrator. Your can find your Research Finance Administrator at https://www.ucl.ac.uk/finance/research/rs-contacts.php by entering your department
Please report any queries concerning the student data shown on the profile page to:

Email: portico-services@ucl.ac.uk

Help Desk: http://www.ucl.ac.uk/ras/portico/helpdesk
Publication Detail
Prevention of Photoreceptor Cell Loss in a Cln6nclf Mouse Model of Batten Disease Requires CLN6 Gene Transfer to Bipolar Cells
  • Publication Type:
    Journal article
  • Publication Sub Type:
    Article
  • Authors:
    Kleine Holthaus S-M, Ribeiro J, Abelleira-Hervas L, Pearson RA, Duran Y, Georgiadis A, Sampson RD, Rizzi M, Hoke J, Maswood R, Azam S, Luhmann UFO, Smith AJ, Mole SE, Ali RR
  • Publisher:
    Nature Publishing Group
  • Publication date:
    02/05/2018
  • Journal:
    Molecular Therapy
  • Medium:
    Print-Electronic
  • Status:
    Published
  • Print ISSN:
    1525-0016
  • Language:
    eng
  • Addresses:
    Department of Genetics, UCL Institute of Ophthalmology, 11-43 Bath Street, London EC1V 9EL, UK; MRC Laboratory for Molecular Cell Biology, University College London, Gower Street, London WC1E 6BT, UK.
Abstract
The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. We found that, although Cln6nclf mice presented mainly with photoreceptor degeneration, supplementation of CLN6 in photoreceptors was not beneficial. Because the level of CLN6 is low in photoreceptors but high in bipolar cells (retinal interneurons that are only lost in Cln6-deficient mice at late disease stages), we explored the therapeutic effects of delivering CLN6 to bipolar cells using adeno-associated virus (AAV) serotype 7m8. Bipolar cell-specific expression of CLN6 slowed significantly the loss of photoreceptor function and photoreceptor cells. This study shows that the deficiency of a gene normally expressed in bipolar cells can cause the loss of photoreceptors and that this can be prevented by bipolar cell-directed treatment.
Publication data is maintained in RPS. Visit https://rps.ucl.ac.uk
 More search options
UCL Researchers Show More
Author
Institute of Ophthalmology
Author
Institute of Ophthalmology
Author
Genetics & Genomic Medicine Dept
Author
Institute of Ophthalmology
Author
Institute of Ophthalmology
University College London - Gower Street - London - WC1E 6BT Tel:+44 (0)20 7679 2000

© UCL 1999–2011

Search by