Cyclic nucleotide signaling as a drug target in retinitis pigmentosa.

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal degenerative diseases caused by mutations in over 90 genes. The complexity of its genetic background and economic barriers limit the broad application of targeted gene therapies. Therefore, general pharmacological strategies to slow disease progression, regardless of the underlying mutation, are needed. Cyclic nucleotide second messengers, such as cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP), are important for normal retinal function. This includes phototransduction, for which cGMP signaling is essential. Dysregulation of the cyclic nucleotide systems is associated with retinal degeneration, and the inhibition of cGMP or cAMP signaling has shown beneficial effects in several retinal degeneration disease models. Here, we propose these systems as drug targets for RP. Impact statement This perspective proposes targeting cyclic nucleotide signaling (cGMP and cAMP) as a mutation-independent therapeutic strategy for retinitis pigmentosa, offering broad potential for disease-modifying treatment potentially through drug repurposing and novel drug delivery systems.