Loss of Cone and Reduction in Rod ERG Responses in the Guanylyl Cyclase-E (GC-E) Deficient Mouse
Guanylyl cyclase-E (GC-E), which is specifically expressed in the retina, has been proposed as critical for normal vision. Mutations within the human homolog of the rodent GC-E gene have been reported in patients with Leber congenital amaurosis (LCA) and in patients with cone-rod dystrophy (CORD6). We have recently produced a mouse genetic model lacking the GC-E gene, and have recorded electroretinograms (ERGs) from mice at different ages. Rod ERGs to flashes over a 6 log unit range were recorded from 18 GC-E −/−, 4 GC-E +/−, and 30 GC-E +/+ mice. Derived parameters were used to assess activation and inactivation stages of transduction, inner retinal function, and cone system activity.
GC-E +/− mice were indistinguishable from normal in all measures. In GC-E −/− mice, the most striking abnormality was a severe reduction in the cone ERG by 3–5 wks of age and a complete absence of a detectable cone ERG in mice >8 wks. An early loss of cones or a failure of cones to develop was confirmed by histological analysis. The maximum rod photoresponse amplitude (Rm) was 70% lower than normal at 3–5 wks despite a normal histological appearance of rods. Recovery from activation, as assessed by a double-flash technique, was more rapid in GC-E −/− than in wild-type mice. Reductions in b-wave amplitude at all ages were accompanied by a shortening of b-wave implicit time.
These findings suggest that GC-E is critical for the survival of cone, but not rod, photoreceptors.
KeywordsRetinitis Pigmentosa Implicit Time Guanylyl Cyclase Cone Response Retinal Illuminance
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