title: Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.
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.
authors.affiliation: School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nivison-Smith
authors.affiliation: School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Optometry and Vision Science, UNSW Australia, Sydney, New South Wales, Australia; Centre for Eye Health, Sydney, New South Wales, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Whatham
authors.affiliation: Department of Optometry and Vision Sciences, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Bang V
authors.initials: BV
authors.lastname: Bui
authors.affiliation: Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: Erica L
authors.initials: EL
authors.lastname: Fletcher
authors.affiliation: Department of Optometry and Vision Science, University of Auckland, Auckland, New Zealand.
authors.forename: Monica L
authors.initials: ML
authors.lastname: Acosta
authors.affiliation: School 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.
authors.forename: Michael
authors.initials: M
authors.lastname: Kalloniatis
mesh_terms: D000818:Animals; D045304:Cytochromes c / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004596:Electroretinography / Q000187:drug effects*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006579:Heterozygote; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D012160:Retina / Q000503:physiopathology*; D051245:Retinal Bipolar Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012174:Retinitis Pigmentosa / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*
chemical_list: D005904:Glial Fibrillary Acidic Protein; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D045304:Cytochromes c; D000068677:Sildenafil Citrate
keywords: Retinitis Pigmentosa; electroretinogram; rd1 mouse; retinal degeneration carriers; sildenafil