Fig. 1.

Interplay of cGMP and Ca²⁺ in photoreceptor outer segments. In darkness, Ca²⁺ prevents guanylyl cyclase–activating protein (GCAP) from activating retinal guanylyl cyclase (GC). GC produces cGMP, which opens the cyclic nucleotide–gated channel (CNGC), allowing for influx of Ca²⁺. In light, phototransduction leads to activation of phosphodiesterase-6 (PDE6), which hydrolyses cGMP, closing CNGC and stopping Ca²⁺ influx. This in turn leads to disinhibition of cGMP synthesis. Mutations in genes encoding for any of these proteins lead to dysregulation of cGMP and Ca²⁺ homoeostasis and can cause retinal degeneration (RD)