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Published on: May 6, 2015
Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina
Janise D Deming1, Joseph S Pak1, Jung-A Shin2
1Mary D. Allen Laboratory for Vision Research, Department of Ophthalmology, Keck School of Medicine of the University of Southern California, USC Eye Institute, Los Angeles, California, United States.
Purpose:
Previous studies discovered cone phototransduction shutoff occurs normally for Arr1-/- and Arr4-/-; however, it is defective when both visual arrestins are simultaneously not expressed (Arr1-/-Arr4-/-). We investigated the roles of visual arrestins in an all-cone retina (Nrl-/-) since each arrestin has differential effects on visual function, including ARR1 for normal light adaptation, and ARR4 for normal contrast sensitivity and visual acuity.
Methods:
We examined Nrl-/-, Nrl-/-Arr1-/-, Nrl-/-Arr4-/-, and Nrl-/-Arr1-/-Arr4-/- mice with photopic electroretinography (ERG) to assess light adaptation and retinal responses, immunoblot and immunohistochemical localization analysis to measure retinal expression levels of M- and S-opsin, and optokinetic tracking (OKT) to measure the visual acuity and contrast sensitivity.
Results:
Study results indicated that Nrl-/- and Nrl-/-Arr4-/- mice light adapted normally, while Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- mice did not. Photopic ERG a-wave, b-wave, and flicker amplitudes followed a general pattern in which Nrl-/-Arr4-/- amplitudes were higher than the amplitudes of Nrl-/-, while the amplitudes of Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- were lower. All three visual arrestin knockouts had faster implicit times than Nrl-/- mice. M-opsin expression is lower when ARR1 is not expressed, while S-opsin expression is lower when ARR4 is not expressed. Although M-opsin expression is mislocalized throughout the photoreceptor cells, S-opsin is confined to the outer segments in all genotypes. Contrast sensitivity is decreased when ARR4 is not expressed, while visual acuity was normal except in Nrl-/-Arr1-/-Arr4-/-.
Conclusions:
Based on the opposite visual phenotypes in an all-cone retina in the Nrl-/-Arr1-/- and Nrl-/-Arr4-/- mice, we conclude that ARR1 and ARR4 perform unique modulatory roles in cone photoreceptors.
Insights
Visual arrestin 1 (ARR1) and visual arrestin 4 (ARR4) have distinct roles in cone photoreceptors. Loss of ARR1 impairs light adaptation, while loss of ARR4 affects contrast sensitivity in mice.
Area of Science:
- Ophthalmology
- Vision Science
- Photoreceptor Biology
Background:
- Cone phototransduction is crucial for vision in bright light.
- Visual arrestins (ARR1 and ARR4) modulate photoreceptor G protein-coupled receptor signaling.
- Previous studies showed normal cone phototransduction shutoff in Arr1-/- and Arr4-/- mice, but defects in Arr1-/-Arr4-/- mice.
Purpose of the Study:
- To investigate the specific roles of visual arrestins (ARR1 and ARR4) in an all-cone retina (Nrl-/- mice).
- To determine the differential effects of ARR1 and ARR4 on light adaptation, contrast sensitivity, and visual acuity.
Main Methods:
- Utilized Nrl-/-, Nrl-/-Arr1-/-, Nrl-/-Arr4-/-, and Nrl-/-Arr1-/-Arr4-/- mouse models.
- Performed photopic electroretinography (ERG) to assess light adaptation and retinal responses.
- Conducted immunoblotting, immunohistochemistry, and optokinetic tracking (OKT) to analyze opsin expression and visual functions.
Main Results:
- Nrl-/- and Nrl-/-Arr4-/- mice exhibited normal light adaptation, unlike Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- mice.
- Absence of ARR1 reduced M-opsin expression and impaired light adaptation, while absence of ARR4 reduced S-opsin expression and decreased contrast sensitivity.
- Photopic ERG amplitudes were generally higher in Nrl-/-Arr4-/- mice compared to Nrl-/- mice, and lower in Nrl-/-Arr1-/- and Nrl-/-Arr1-/-Arr4-/- mice.
Conclusions:
- ARR1 and ARR4 play distinct and essential modulatory roles in cone photoreceptor function.
- The absence of ARR1 primarily affects light adaptation, while the absence of ARR4 impacts contrast sensitivity.
- These findings highlight the unique contributions of each visual arrestin in mediating visual perception.
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