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Bruce M. Brown, Moon K. Kim, Moe H. Aung, Lawrence L. Rife, Machelle T. Pardue, Cheryl M. Craft; Abnormal Photopic ERG Responses and Defective Contrast Sensitivity in Cone Arrestin 4 Knockout Mice Reveal Potential Regulatory Functions. Invest. Ophthalmol. Vis. Sci. 2012;53(14):760.
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© ARVO (1962-2015); The Authors (2016-present)
At least one visual Arrestin, Arr1 or Arr4, must be expressed in a single mouse cone for normal inactivation of phototransduction and photopic recovery of light activated, phosphorylated S- & M-opsins (Nikonov et al., Neuron 2008; 59:462). Utilizing Arr1, Arr4, or Arr1Arr4 double knockouts (DKO) on either WT or Nrl-/- background, we examined electrophysiological and behavioral phenotypes.
Electroretinography (ERG) was used to measure the retinal response to single flash, flicker (0.2 to 20 Hz), and chromatic stimuli (340 & 540 nm) of various intensities using a Grass Xenon PS22 (-1.59 to 2.01 log cd s/m2) or Ganzfeld (-3.4 to 2.9 log cd s/m2) stimulator under dark- or light-adapted conditions. Optokinetic tracking (OKT) was used to measure visual acuity (VA) and contrast sensitivity (CS) by recording the threshold response to varying spatial frequencies and contrasts.
In response to bright flicker stimuli delivered through a fiber optic from the Grass stimulator using flicker frequency under light adapted conditions, the Arr4-/- mice on both backgrounds had significantly increased b-wave amplitudes compared with all other genotypes. In contrast, increasing single flash Ganzfeld stimulation showed decreased responses from Arr1-/- and Arr4-/- genotypes on both backgrounds compared with controls (WT or Nrl-/-). Ganzfeld flicker stimuli only revealed a reduction in amplitude from DKOs on both backgrounds. Nrl-/- Arr1-/- retinas responded with higher amplitudes to UV stimuli compared with Nrl-/-Arr4-/- or Nrl-/- genotypes; green stimuli did not elicit any differences. Visual acuity was decreased in Arr4-/- and DKO genotypes on both backgrounds, while contrast sensitivity was greatly diminished in Arr4-/- mice compared with Arr1-/- or WT.
Our ERG and behavioral studies illustrate the divergence in visual arrestins functional roles to process cellular signals in cones downstream of the phototransduction cascade. Elevated photopic ERG responses recorded in genotypes lacking Arr4 suggest that Arr4 plays an essential function in limiting photoreceptor responses and balancing normal contrast sensitivity. Elevated ERG photopic responses in Arr4-/- mice, as seen under higher intensity flash conditions, suggest the animal is less capable of regulating light signals. Investigations into the potential interaction of visual arrestins with dopamine to elicit this response are presented (Craft et al., ARVO 2012).
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