GUCY2D encodes retinal guanylate cylase-1 (retGC1), a protein that plays a pivotal role in the recovery phase of phototransduction. Mutations in GUCY2D are associated with a leading cause of recessive Leber congenital amaurosis (LCA1). Patients present within the first year of life with aberrant or unrecordable electroretinogram (ERG), nystagmus and a relatively normal fundus. Aside from abnormalities in the outer segments of foveal cones and, in some patients, foveal cone loss, LCA1 patients retain normal retinal laminar architecture suggesting they may be good candidates for gene replacement therapy. Several animal models of LCA1, both naturally occurring and engineered, have been characterized and provide valuable tools for translational studies. This mini-review will summarize the phenotypes of these models and describe how each has been instrumental in proof of concept studies to develop a gene replacement therapy for GUCY2D-LCA1.
Keywords: AAV; GC1; GUCY2D; Gene therapy; LCA1; Leber congenital amaurosis; RetGC1; Retinal guanylate cyclase.