Light-driven cone arrestin translocation in cones of postnatal guanylate cyclase-1 knockout mouse retina treated with AAV-GC1.

Purpose: Cone function and survival are compromised in the guanylate cyclase-1 (GC1) knockout mouse. Disruption of the light-driven translocation of cone arrestin is one of the phenotypes of cone cells in this retina: the cone arrestin in these cells is localized to the outer segments and synaptic terminals, regardless of the state of light adaptation. The purpose of this study was to determine whether the expression of GC1 restores cone arrestin translocation in the cone cells of postnatal GC1 knockout mouse retina.

Efficiency of lentiviral transduction during development in normal and rd mice.

Purpose: To compare the transduction efficiency of a lentiviral vector in the retina of normal mice and retinal degenerative (rd) mice following subretinal injection at various postnatal ages.

Methods: Subretinal injections of lentiviral vector (pHR-CMV-GFP, 107IU/ml) were performed in normal (C57/6J) and rd mice on postnatal days P1 to P7 using a trans-scleral method and on days P14-P35 by a trans-corneal method. One to six weeks later the eyes were prepared for histological analysis.

Lentiviral expression of retinal guanylate cyclase-1 (RetGC1) restores vision in an avian model of childhood blindness.

Background: Leber congenital amaurosis (LCA) is a genetically heterogeneous group of retinal diseases that cause congenital blindness in infants and children. Mutations in the GUCY2D gene that encodes retinal guanylate cyclase-1 (retGC1) were the first to be linked to this disease group (LCA type 1 [LCA1]) and account for 10%-20% of LCA cases. These mutations disrupt synthesis of cGMP in photoreceptor cells, a key second messenger required for function of these cells.