@article{64e70fc514324f7f8ef9eea0ae33e9a6,
title = "Arrestin 1 and cone arrestin 4 have unique roles in visual function in an all-cone mouse retina",
abstract = "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.",
keywords = "Cone function, Cone opsins, NRL knockout, Visual arrestins",
author = "Deming, {Janise D.} and Pak, {Joseph S.} and Shin, {Jung A.} and Brown, {Bruce M.} and Kim, {Moon K.} and Aung, {Moe H.} and Lee, {Eun Jin} and Pardue, {Machelle T.} and Craft, {Cheryl Mae}",
note = "Funding Information: The authors thank Mary D. Allen (1911-2011) for her lifetime support of Doheny Eye Institute and our vision research program, as well as members and USC undergraduate students in our Mary D. Allen Laboratory for Vision Research for their technical contributions, including Lawrence Rife for excellent technical assistance in ERG recordings, Ernesto Barron for his assistance with confocal image training, and Ruqayyah Malik and Andrew Vargus for their assistance in preparing final figures. Supported by Doheny Eye Institute{\textquoteright}s Inaugural Mary D. Allen Endowed Chair in Vision Research (CMC), and in part by grant awards from the National Institutes of Health-NEI R01-EY015851 (CMC), R01-EY016435 (MTP), EY03040 (Doheny Eye Institute, NEI Core Grant), Department of Veterans Affairs (MTP) and Research to Prevent Blindness (USC Ophthalmology), and the Mary D. Allen Foundation (CMC, JDD, JSP), Dorie Miller (JDD, JSP), William Hansen Sandberg Memorial Foundation (JDD, JSP), and Tony Gray Foundation (JDD). Funding Information: The authors thank Mary D. Allen (1911–2011) for her lifetime support of Doheny Eye Institute and our vision research program, as well as members and USC undergraduate students in our Mary D. Allen Laboratory for Vision Research for their technical contributions, including Lawrence Rife for excellent technical assistance in ERG recordings, Ernesto Barron for his assistance with confocal image training, and Ruqayyah Malik and Andrew Vargus for their assistance in preparing final figures. Supported by Doheny Eye Institute{\textquoteright}s Inaugural Mary D. Allen Endowed Chair in Vision Research (CMC), and in part by grant awards from the National Institutes of Health-NEI R01-EY015851 (CMC), R01-EY016435 (MTP), EY03040 (Doheny Eye Institute, NEI Core Grant), Department of Veterans Affairs (MTP) and Research to Prevent Blindness (USC Ophthalmology), and the Mary D. Allen Foundation (CMC, JDD, JSP), Dorie Miller (JDD, JSP), William Hansen Sandberg Memorial Foundation (JDD, JSP), and Tony Gray Foundation (JDD). Disclosure: J.D. Deming, None; J.S. Pak, None; J. Shin, None; B.M. Brown, None; M.K. Kim, None; M.H. Aung, None; E.-J. Lee, None; M.T. Pardue, None; C.M. Craft, None Publisher Copyright: {\textcopyright} 2015 The Association for Research in Vision and Ophthalmology, Inc.",
year = "2015",
month = dec,
doi = "10.1167/iovs.15-17832",
language = "English",
volume = "56",
pages = "7618--7628",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "13",
}