4.6 Article

Visual Cone Arrestin 4 Contributes to Visual Function and Cone Health

期刊

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
卷 56, 期 9, 页码 5407-5416

出版社

ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.15-16647

关键词

cone arrestin; visual function; cones; age-related cone degeneration

资金

  1. NEI NIH HHS [R01-EY016435, EY03040, R01 EY016435, R01 EY015851, P30 EY003040, R01-EY015851] Funding Source: Medline
  2. NIGMS NIH HHS [T32 GM008169] Funding Source: Medline

向作者/读者索取更多资源

PURPOSE. Visual arrestins (ARR) play a critical role in shutoff of rod and cone photo-transduction. 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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.6
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据