May 2007
Volume 48, Issue 13
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ARVO Annual Meeting Abstract  |   May 2007
Assessment of Longterm Neuroprotection by CNTF Gene Transfer in a Mouse Inherited Retinal Degeneration
R. E. MacLaren; P. K. Buch; A. Georgiadis; M. Tschernutter; R. A. Pearson; A. J. Smith; R. R. Ali
Author Affiliations & Notes
  • R. E. MacLaren
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
    Vitreoretinal Service, Moorfields Eye Hospital, London, United Kingdom
  • P. K. Buch
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • A. Georgiadis
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • M. Tschernutter
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • R. A. Pearson
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • A. J. Smith
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • R. R. Ali
    Division of Molecular Therapy, UCL Institute of Ophthalmology, London, United Kingdom
  • Footnotes
    Commercial Relationships R.E. MacLaren, None; P.K. Buch, None; A. Georgiadis, None; M. Tschernutter, None; R.A. Pearson, None; A.J. Smith, None; R.R. Ali, None.
  • Footnotes
    Support The British Retinitis Pigmentosa Society; The Scottish National Institute for the War Blinded; The Royal Blind Asylum and School; The Health Foundation and the Medical Research Council (UK)
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 3209. doi:
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      R. E. MacLaren, P. K. Buch, A. Georgiadis, M. Tschernutter, R. A. Pearson, A. J. Smith, R. R. Ali; Assessment of Longterm Neuroprotection by CNTF Gene Transfer in a Mouse Inherited Retinal Degeneration. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3209.

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Abstract
 
Purpose:
 

To assess the longterm neuroprotective effects of ciliary neurotrophic factor (CNTF) delivered by gene transfer to the retina in the heterozygous rds mouse (Prph2+/rd2).

 
Methods:
 

Adeno-associated (AAV) gene transfer of CNTF was achieved by intravitreal injection into one eye of seven heterozygous rds mice at weaning The unprocedured fellow eye was used as a control. Mice were assessed by electroretinogram (ERG) at 4 monthly intervals up to 20 months of age. Retinal histology and RT-PCR for peripherin-2 was performed at sacrifice of aged animals.

 
Results:
 

A mean reduction of 45-50% of the ERG a-b wave deflection was noted in the CNTF treated eye compared to controls and this relative drop was maintained up to 20 months such that mean amplitudes declined in parallel. At 20 months, marked outer nuclear layer degeneration appeared similar between CNTF treated and control eyes. Levels of mRNA for peripherin-2 were not significantly different between the two eyes. Immunohistochemistry however showed a marked reduction in cone opsin production in CNTF treated eyes.Results: A mean reduction of 45-50% of the ERG a-b wave deflection was noted in the CNTF treated eye compared to controls and this relative drop was maintained over 18 months such that mean amplitudes declined in parallel. At 18 months outer nuclear layer degeneration appeared similar between CNTF treated or control eyes. Levels of mRNA for peripherin-2 were not significantly different between eyes. Immunohistochemistry however showed a marked reduction in cone opsin production in CNTF treated eyes.(red = L+M cone opsins; green = PNA cone label)  

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Conclusions:
 

CNTF delivered by gene transfer to the inner retina did not confer detectable neuroprotection over the lifetime of this mouse model of slow photoreceptor degeneration. A specific reduction in cone opsins may in part account for the ERG suppression.

 
Keywords: retinal degenerations: hereditary • neuroprotection • gene transfer/gene therapy 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2025 Association for Research in Vision and Ophthalmology.
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