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Publication : Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa.

First Author  Nivison-Smith L Year  2014
Journal  Exp Eye Res Volume  128
Pages  43-56 PubMed ID  25239397
Mgi Jnum  J:230189 Mgi Id  MGI:5755739
Doi  10.1016/j.exer.2014.08.014 Citation  Nivison-Smith L, et al. (2014) Sildenafil alters retinal function in mouse carriers of retinitis pigmentosa. Exp Eye Res 128:43-56
abstractText  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.
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