Investigation of daily four month sildenafil administration on heterozygous carriers of a phosphodiesterase 6 mutation in a canine model of autosomal recessive retinitis pigmentosa
Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy resulting in significant visual deficits and blindness in humans. Autosomal recessive, autosomal dominant, X-linked, maternal, and digenic inheritance patterns encompass the modes of RP inheritance. Phosphodiesterase enzymes hydrolyze intracellular second messengers regulating cell-to-cell interactions. A mutation in the phosphodiesterase type 6 gene, involving the alpha-, beta-, or gamma-subunits, is one of the numerous causes of autosomal recessive retinitis pigmentosa. Several pharmacologic investigations assessing the effect sildenafil, a phosphodiesterase type 5 inhibitor, has on retinal function and vision, as well as genetic investigations in heterozygous individuals for both a phosphodiesterase alpha- and beta-subunit mutation are documented in the literature. We assessed retinal function and vision in dogs heterozygous for a phosphodiesterase type 6 alpha-subunit mutation while receiving sildenafil for four months duration. Low-intensity, dark-adapted, rod-led ERG responses were transiently reduced and a higher threshold response was observed in dogs receiving sildenafil. All ERG alterations were transient and completely reversed at washout. Sildenafil did not have a clinical observed effect on vision. Sildenafil transiently raised the rod-mediated ERG threshold in heterozygous PDE6A mutant and control dogs.
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- In Collections
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Electronic Theses & Dissertations
- Copyright Status
- In Copyright
- Material Type
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Theses
- Authors
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Pierce, Kenneth E.
- Thesis Advisors
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Bartoe, Joshua T.
- Committee Members
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Townsend, Wendy
Petersen-Jones, Simon M.
Hauptman, Joe
- Date
- 2011
- Subjects
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Veterinary ophthalmology
Retinitis pigmentosa
Dogs--Physiology
Sildenafil
Retina
Diseases--Research
Blindness in animals
- Program of Study
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Small Animal Clinical Sciences
- Degree Level
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Masters
- Language
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English
- Pages
- ix, 82 pages
- ISBN
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9781124600987
1124600981
- Permalink
- https://doi.org/doi:10.25335/zskr-v394