Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health.
OBJECTIVE
Visual arrestins (ARR) play a critical role in shutoff of rod and cone phototransduction. When electrophysiological responses are measured for a single mouse cone photoreceptor, ARR1 expression can substitute for ARR4 in cone pigment desensitization; however, each arrestin may also contribute its own, unique role to modulate other cellular functions.


METHODS
A combination of ERG, optokinetic tracking, immunohistochemistry, and immunoblot analysis was used to investigate the retinal phenotypes of Arr4 null mice (Arr4-/-) compared with age-matched control, wild-type mice.


RESULTS
When 2-month-old Arr4-/- mice were compared with wild-type mice, they had diminished visual acuity and contrast sensitivity, yet enhanced ERG flicker response and higher photopic ERG b-wave amplitudes. In contrast, in older Arr4-/- mice, all ERG amplitudes were significantly reduced in magnitude compared with age-matched controls. Furthermore, in older Arr4-/- mice, the total cone numbers decreased and cone opsin protein immunoreactive expression levels were significantly reduced, while overall photoreceptor outer nuclear layer thickness was unchanged.


CONCLUSIONS
Our study demonstrates that Arr4-/- mice display distinct phenotypic differences when compared to controls, suggesting that ARR4 modulates essential functions in high acuity vision and downstream cellular signaling pathways that are not fulfilled or substituted by the coexpression of ARR1, despite its high expression levels in all mouse cones. Without normal ARR4 expression levels, cones slowly degenerate with increasing age, making this a new model to study age-related cone dystrophy.
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.
Janise D
JD
Deming
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.
Joseph S
JS
Pak
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States.
Bruce M
BM
Brown
Rehabilitation Research & Development Center of Excellence, Atlanta VA Medical Center, Decatur, Georgia, United States.
Moon K
MK
Kim
Neuroscience/Ophthalmology, Emory University, Atlanta, Georgia, United States.
Moe H
MH
Aung
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States 4Dornsife College of Letters, Arts and Sciences, Univers.
Yun Sung
YS
Eom
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States 5Department of Anatomy, School of Medicine, Ewha Womans.
Jung-A
JA
Shin
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States 6Department of Biomedical Engineering, University of Sou.
Eun-Jin
EJ
Lee
Rehabilitation Research & Development Center of Excellence, Atlanta VA Medical Center, Decatur, Georgia, United States 3Neuroscience/Ophthalmology, Emory University, Atlanta, Georgia, United States.
Machelle T
MT
Pardue
Mary D. Allen Laboratory for Vision Research, USC Eye Institute, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, Los Angeles, California, United States 7Department of Cell & Neurobiology, Keck School of Medic.
Cheryl Mae
CM
Craft
D000818:Animals; D019393:Arrestin / Q000235:genetics* / Q000378:metabolism; D002452:Cell Count; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D004596:Electroretinography; D005786:Gene Expression Regulation; D015151:Immunoblotting; D007150:Immunohistochemistry; D055537:Light Signal Transduction / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D010641:Phenotype; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology
D019393:Arrestin; D004247:DNA