Rod-specific cGMP phosphodiesterase 6 (PDE6)

Rod-specific cGMP phosphodiesterase 6 (PDE6) is a key enzyme in the visual phototransduction cascade, primarily located in the outer segments of rod photoreceptor cells. It exists as a heterotetrameric complex consisting of two catalytic subunits (alpha and beta) and two inhibitory gamma subunits. Upon light stimulation, the G-protein transducin activates PDE6, which then rapidly hydrolyzes cyclic guanosine monophosphate (cGMP) to 5'-GMP. This decrease in cGMP levels leads to the closure of cGMP-gated cation channels, resulting in cell hyperpolarization and the transmission of visual signals to the brain. Mutations in the genes encoding its subunits (PDE6A, PDE6B, or PDE6G) are a major cause of autosomal recessive retinitis pigmentosa, a degenerative eye disease characterized by night blindness and progressive peripheral vision loss. Additionally, PDE6 is a significant off-target for phosphodiesterase 5 (PDE5) inhibitors like sildenafil, which can cause transient visual disturbances due to their structural similarity to the PDE6 catalytic site.

Other names

PDE6APDE6BPDE6GRod-specific cGMP phosphodiesterasecGMP-specific 3',5'-cyclic phosphodiesteraseRod photoreceptor phosphodiesterase

Phosphodiesterase inhibition; Gene supplementation