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.
Read
