Cyclic-GMP Phosphodiesterase and Calmodulin in Early-Onset Inherited Retinal Degenerations

Cyclic 3´,5´-nucleotide phosphodiesterase catalyzes the hydrolysis of cyclic adenosine 3´,5´-monophosphate or cyclic guanosine 3´,5´-monophosphate (cGMP) to the corresponding 5´-nucleotide. The phosphodiesterase (PDE) enzyme is the only enzyme that can break down or metabolize cyclic nucleotides. Therefore, along with the appropriate cyclase enzymes, PDE is of pivotal importance in controlling the concentration of intracellular messengers. PDE also plays an active role in the regulation of cyclic-nucleotide concentration. This is particularly true in the photoreceptor cell where it may very well have a central role in the visual process. Cyclic nucleotides and PDE inhibitors can damage and destroy retinal rod photoreceptors, although the mechanism is obscure. There is a need to define a method for decreasing the cGMP concentration, possibly through the stimulation of residual PDE activity in the remaining photoreceptor cells.