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Abstract #20412 Published in IGR 10-1
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 AEye 2008; 22: 144-149
OBJECTIVE: We 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. METHODS: Using 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. RESULTS: CDU 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. CONCLUSION: We 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.
Department of Histology, Microbiology and Medical Biotechnologies, University of Padova, Padova, Italy
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
6.11 Bloodflow measurements (Part of: 6 Clinical examination methods)
3.8 Pharmacology (Part of: 3 Laboratory methods)
