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Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.

ABSTRACT: 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.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.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-/-.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.

SUBMITTER: Deming JD

PROVIDER: S-EPMC4669854 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

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Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.

Deming Janise D JD Pak Joseph S JS Shin Jung-A JA Brown Bruce M BM Kim Moon K MK Aung Moe H MH Lee Eun-Jin EJ Pardue Machelle T MT Craft Cheryl Mae CM

Investigative ophthalmology & visual science 20151201 13

<h4>Purpose</h4>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.<h4>Methods</h4>We examined Nrl-/-, ...[more]

PMID: 26624493

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Project description:PurposeCone function and survival are compromised in the guanylate cyclase-1 (GC1) knockout mouse. Disruption of the light-driven translocation of cone arrestin is one of the phenotypes of cone cells in this retina: the cone arrestin in these cells is localized to the outer segments and synaptic terminals, regardless of the state of light adaptation. The purpose of this study was to determine whether the expression of GC1 restores cone arrestin translocation in the cone cells of postnatal GC1 knockout mouse retina.MethodsSubretinal injections of AAV-GC1 were performed on 3-week-old GC1 KO mice. Electroretinographic and immunohistochemical analyses of treated retinas were carried out 5 weeks after injection. GC1 and cone arrestin antibodies were used to identify photoreceptors transduced by the AAV vector and to localize cone arrestin within cone cells, respectively.ResultsTreatment of GC1 knockout retinas with AAV-GC1 restored the light-driven translocation of cone arrestin in transduced cone cells. Staining patterns for cone arrestin in transduced and wild-type cone cells were indistinguishable after dark and light adaptation. In dark-adapted retinas, cone arrestin was distributed throughout the subcellular compartments of the cone cells. In light-adapted retinas, cone arrestin was concentrated in the cone outer segments. Successful restoration of cone arrestin translocation did not translate to a restoration of cone ERG responses, which remained undetectable in the treated retinas.ConclusionsAAV-mediated expression of GC1 in a subpopulation of cone cells in postnatal GC1 knockout retina restores light-driven translocation of cone arrestin in these cells. These findings, which show that fully developed cone cells that have developed in the absence of GC1 can respond to viral-mediated expression of this enzyme, support further analysis of this animal model of Leber congenital amaurosis type 1 (LCA1), a disease that results from null mutations in the gene encoding this enzyme.

Dataset Information

Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.

Publications

Arrestin 1 and Cone Arrestin 4 Have Unique Roles in Visual Function in an All-Cone Mouse Retina.

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