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Loss of Cone and Reduction in Rod ERG Responses in the Guanylyl Cyclase-E (GC-E) Deficient Mouse

  • David G. Birch
  • Ruey-Bing Yang
  • Susan W. Robinson
  • David L. Garbers

Abstract

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.

Keywords

Retinitis Pigmentosa Implicit Time Guanylyl Cyclase Cone Response Retinal Illuminance 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Kluwer Academic / Plenum Publishers 1999

Authors and Affiliations

  • David G. Birch
    • 1
    • 2
  • Ruey-Bing Yang
    • 3
  • Susan W. Robinson
    • 3
    • 4
  • David L. Garbers
    • 3
    • 4
  1. 1.Retina Foundation of the SouthwestDallas
  2. 2.Department of OphthalmologyUniversity of Texas Southwestern Medical CenterDallas
  3. 3.Department of PharmacologyUniversity of Texas Southwestern Medical CenterDallas
  4. 4.the Howard Hughes Medical InstituteUniversity of Texas Southwestern Medical CenterDallas

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