Visual Arrestin 1 contributes to cone photoreceptor survival and light adaptation.
OBJECTIVE
To evaluate morphologic and functional contributions of Arrestin 1 (Arr1) and Arrestin 4 (Arr4) in cone photoreceptors, the authors examined the phenotypes of visual arrestin knockout mice (Arr1(-/-), Arr4(-/-), Arr1(-/-)Arr4(-/-) [Arr-DKO]) reared in darkness.


METHODS
Retinal rods and cones were evaluated in wild-type (WT), Arr1(-/-), Arr4(-/-), and Arr-DKO mice using quantitative morphologic analysis, immunoblot, immunohistochemistry, TUNEL, and electroretinographic (ERG) techniques.


RESULTS
Compared with either Arr4(-/-) or WT, Arr1(-/-) and Arr-DKO mice had increased apoptotic nuclei in their retinal outer nuclear layer (ONL) at postnatal day (P) 22. By P60, cone density was significantly diminished, but the ONL appeared normal. After 1 minute of background illumination, cone ERG b-wave amplitudes were similar in WT and all Arr KO mice. However, by 3 minutes and continuing through 15 minutes of light adaptation, the cone b-wave amplitudes of WT and Arr4(-/-) mice increased significantly over those of the Arr1(-/-) and Arr-DKO mice, which demonstrated no cone b-wave amplitude increase. In contrast, ERG flicker analysis after the 15-minute light adaptation period demonstrated no loss in amplitude for either Arr1(-/-) or Arr4(-/-) mice, whereas Arr-DKO had significantly lower amplitudes. When Arr1 expression was restored in Arr1(-/-) mice (+p48(Arr1-/-)), normal cone density and light-adapted ERG b-wave amplitudes were observed.


CONCLUSIONS
In the adult dark-reared Arr1(-/-) and Arr-DKO mice, viable cones diminish over time. Arr1 expression is essential for cone photoreceptor survival and light adaptation, whereas either Arr1 or Arr4 is necessary for maintaining normal flicker responses.
Brown
Bruce M
BM
Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033-9224, USA.
Ramirez
Teresa
T
Rife
Lawrence
L
Craft
Cheryl M
CM
D000221:Adaptation, Ocular / Q000502:physiology*; D000818:Animals; D019390:Arrestins / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D004596:Electroretinography; D019084:Fluorescent Antibody Technique, Indirect; D005838:Genotype; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D016133:Polymerase Chain Reaction; D017949:Retinal Cone Photoreceptor Cells / Q000166:cytology*; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins
C000605255:Arrb1 protein, mouse; D019390:Arrestins; D000071559:beta-Arrestin 1; D000071557:beta-Arrestins