Retinal guanylyl cyclase 1 (GUCY2D) (GUCY2D)

Retinal guanylyl cyclase 1 (GUCY2D) is a membrane-bound enzyme primarily expressed in the outer segments of rod and cone photoreceptor cells in the retina (UniProt Q02846). It plays a critical role in the phototransduction cascade by synthesizing cyclic guanosine monophosphate (cGMP) from GTP, which is essential for keeping cyclic nucleotide-gated (CNG) channels open and maintaining the photoreceptor's dark state (MedlinePlus, 2022). Mutations in the GUCY2D gene lead to severe inherited retinal dystrophies, most notably Leber Congenital Amaurosis type 1 (LCA1), characterized by early-onset blindness due to the inability of photoreceptors to recover after light exposure (NIH, 2020). Therapeutic strategies currently focus on gene augmentation therapy, such as ATSN-101, which uses adeno-associated virus (AAV) vectors to deliver functional copies of the GUCY2D gene to the retina (Atsena Therapeutics, 2022). Clinical trials have shown promising results in restoring visual sensitivity and mobility in patients with LCA1 (Jacobson et al., 2021). The enzyme's activity is regulated by calcium-sensing proteins called guanylate cyclase-activating proteins (GCAPs), which modulate cGMP production in response to light-induced changes in intracellular calcium levels (Gene.Vision, 2020).

Other names

RetGC1GC-EROS-GC1LCA1CORD6CYGDGUC1A4GUC2DGuanylate cyclase 2D, retinal

Gene augmentation therapy delivering a functional copy of the GUCY2D gene to photoreceptor cells via an adeno-associated virus (AAV) vector to restore cGMP synthesis and phototransduction recovery.