Arrestin 1 and cone arrestin 4 have unique roles in visual function in an all-cone mouse retina

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, bwave, 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 Sopsin 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.