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Expression of the PDE5 enzyme on human retinal tissue: new aspects of PDE5 inhibitors ocular side effects.

Foresta C, Caretta N, Zuccarello D, Poletti A, Biagioli A, Caretti L, Galan A

1Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy.

ObjectiveWe tested the effect of two phosphodiesterase type-5 (PDE5) inhibitors, sildenafil and tadalafil, on ophthalmic artery (OA) blood flow velocity and investigated the presence of the PDE5 enzyme on human retinal tissue in comparison with the PDE6 enzyme localization.MethodsUsing Colour Doppler ultrasonography (CDU) we investigated, in 30 healthy young subjects (27.8 years of age; range, 24.3-33.7 years), the effects of a single oral dose of sildenafil (100 mg), tadalafil (20 mg), and placebo on OA blood flow velocity. Western blot for PDE6 and PDE5 protein expression was performed on frozen samples of human retina, testis, sperm, skin, and corpus cavernosum. Immunohistochemistry was performed on two ocular globes from dead donors.ResultsCDU showed a relationship between the administration of PDE5 inhibitors and OA blood flow velocity modifications in a time-dependent manner. Western blot and immunohistochemical analysis showed PDE6 and PDE5 presence in human retinal tissue and gave a map of its distribution.ConclusionWe demonstrated that (a) tadalafil and sildenafil are able to modify the OA flux in a time-dependent manner; (b) the PDE5 enzyme is expressed on retinal and choroid vasculature (smooth muscle and endothelial cells), on ganglion and bipolar cells; (c) human retinal tissues express the PDE6 enzyme in the rod and cone photoreceptors; (d) visual side effects after PDE5 inhibitors administration may be linked to a specific effect on the PDE5 enzyme; and (e) the PDE5 enzyme may have a physiologic role on ganglion and bipolar cells that need to be further investigated.Eye (2008) 22, 144-149; doi:10.1038/sj.eye.6702908; published online 22 June 2007.

Published 17 January 2008 in Eye, 22(1): 144-9.
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