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S. M. Petersen-Jones, G. C. Shaw, F. Montiani-Ferreira; Drug Dissection of the RGE Chicken Electroretinogram Suggests That GNB3 Plays a Role in Inner Retinal Function. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1939.
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The rge chicken has a mutation in GNB3 (cone beta transducin) predicted to reduce the function of the protein. Affected chicks have an elevated ERG response threshold and a delayed down slope of the a-wave. However, they also have additional ERG changes not explained by the function of GNB3 in cone phototransduction; they develop a supernormal b-wave at bright stimulus intensity that is not blocked by APB and have a lack of oscillatory potentials. These abnormalities suggest that GNB3 may play a role in inner retinal function. This study was undertaken to further investigate this possibility.
The following drugs, singly or in combination, were used to dissect the ERG: Aspartate, APB, PDA and NMDA. Dark and light adapted flash ERG and long flash ERGs were recorded pre and post injection.
Aspartate eliminated the b-wave from both mutant and control birds leaving the PIII response. APB suppressed the control but not the mutant chick b-wave. In control chicks PDA removed a negative component of the light-adapted a-wave and eliminated the photopic hill effect of the b-wave intensity:response curve. It also enhanced the b-wave of the long flash ERG and suppressed the d-wave. The effect of PDA on the mutant bird ERG was quite different; it removed a faster negative component of the a-wave leaving an a-wave with a shallower slope and increased implicit time. It also suppressed the supernormal b-wave. The effect of PDA on the long flash of the mutant bird was opposite to that in controls. In mutants, the b-wave was suppressed and the d-wave enhanced. NMDA tended to reduce the b-wave in the mutant bird flash and long-flash ERG.
As anticipated, given the known function of GNB3 in cone phototransduction and the cone dominance of the chicken retina, mutant chicks have reduced retinal sensitivity. They also have abnormalities in inner retinal pathways. The APB resistant supernormal b-wave is removed by aspartate, indicating it is inner retina in origin. It is also suppressed by PDA and NMDA. PDA blocks transmission between photoreceptors and OFF bipolar cells and horizontal cells, and between bipolar and third order neurons. NMDA blocks the responses of third order neurons. The results suggest that GNB3 mutant birds have a lack of normal ON bipolar function, and an abnormality in the OFF pathway and/or possibly also third order neuron responses. Further studies to elucidate the role of GNB3 in inner retinal signaling are warranted.
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