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Exp Eye Res. 2014 Nov;128:43-56. doi: 10.1016/j.exer.2014.08.014. Epub 2014 Sep 17.

Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

Author information

  • 1School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia.
  • 2School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia; Centre for Eye Health, Sydney, New South Wales, Australia.
  • 3Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.
  • 4Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
  • 5Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand.
  • 6School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia; Centre for Eye Health, Sydney, New South Wales, Australia; Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia; Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand. Electronic address: m.kalloniatis@unsw.edu.au.

Abstract

Sildenafil, the active ingredient in Viagra, has been reported to cause transient visual disturbance from inhibition of phosphodiesterase 6 (PDE6), a key enzyme in the visual phototransduction pathway. This study investigated the effects of sildenafil on the rd1(+/-) mouse, a model for carriers of Retinitis Pigmentosa which exhibit normal vision but may have a lower threshold for cellular stress caused by sildenafil due to a heterozygous mutation in PDE6. Sildenafil caused a dose-dependent decrease in electroretinogram (ERG) responses of normal mice which mostly recovered two days post administration. In contrast, rd1(+/-) mice exhibited a significantly reduced photoreceptor and a supernormal bipolar cell response to sildenafil within 1 h of treatment. Carrier mice retinae took two weeks to return to baseline levels suggesting sildenafil has direct effects on both the inner and outer retina and these effects differ significantly between normal and carrier mice. Anatomically, an increase in expression of the early apoptotic marker, cytochrome C in rd1(+/-) mice indicated that the effects of sildenafil on visual function may lead to degeneration. The results of this study are significant considering approximately 1 in 50 people are likely to be carriers of recessive traits leading to retinal degeneration.

Copyright © 2014 Elsevier Ltd. All rights reserved.

KEYWORDS:

Retinitis Pigmentosa; electroretinogram; rd1 mouse; retinal degeneration carriers; sildenafil

PMID:
25239397
[PubMed - indexed for MEDLINE]
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