The role of OPN5 in extraocular circadian photoentrainment in mammals

OPN5 在哺乳动物眼外昼夜光诱导中的作用

基本信息

  • 批准号:
    10005374
  • 负责人:
  • 金额:
    $ 37.07万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-09-15 至 2022-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary/Abstract The 24 hour solar cycle is one of the most predictable, yet potentially damaging, aspects of life on Earth. Because of this, most animals utilize molecular circadian clocks which anticipate the rising sun and are prepared when the light is at its most UV-enriched. There are various ways in which this is achieved at the behavioral, anatomic, and physiologic levels. OPN5 is an opsin which is maximally sensitive to short- wavelength light. Recently, we found that OPN5 is a critical element in the mammalian retina’s ability to synchronize its local circadian rhythms to light cycles. The skin and the cornea are also daily exposed to sunlight in most animals, and both tissues contain robust, autonomous circadian clocks. We and others have observed the expression of OPN5 in both of these tissues. This proposal aims to characterize the role of these extraretinal OPN5 photoreceptors on the circadian rhythms of these tissues. Specifically, the aim of this project is to identify the specific cells in the skin and cornea that express OPN5, characterize their photic response, characterize the mechanism these cells use to disseminate photic information, and characterize the circadian nature of the light response that these tissues display. Using a mouse line from which a circadian luciferase reporter can be measured as a representation of clock gene expression, we have demonstrated that clocks in both skin and corneas can be synchronized by light and that this circadian photoreception is regulated by OPN5. This circadian reporter will be used to monitor tissues in culture, and a mouse line which includes a fluorescent protein only in OPN5 expressing cells will allow us to ascertain the precise identity of the extraretinal photoreceptor cells. Lastly, this proposal seeks to link the expression of extraocular photoreception to potential health risks. Skin, in particular, has been shown to have precise times of day when it is most vulnerable to UV light for development of skin cancer and erythema. This proposal will examine the role OPN5 plays in controlling timing of cell division, acute responses to UV light, the sensitivity during development, and the global transcriptional landscape of the skin and cornea. By analyzing the molecular state of tissues exposed to specific light conditions at various times of day we will gain a better understanding of the ways mammalian cells cope with high energy light, and we will begin to understand the way they use OPN5 to regulate circadian clocks to anticipate photic changes in their environment.
项目总结/摘要 24小时的太阳活动周期是地球上生命最可预测的,但也是最具潜在破坏性的方面。 正因为如此,大多数动物利用分子生物钟来预测太阳的升起, 当光线紫外线最丰富时准备。有各种方法可以实现这一点, 行为、解剖和生理水平。OPN 5是一种视蛋白,其对短- 波长光最近,我们发现OPN 5是哺乳动物视网膜的一个关键因素, 使当地的昼夜节律与光周期同步。皮肤和角膜也每天暴露于 这两种组织都含有强大的自主生物钟。我们和其他人 观察到OPN 5在这两种组织中的表达。该提案旨在描述 这些视网膜外OPN 5光感受器对这些组织的昼夜节律的作用。具体地说, 该项目的目的是鉴定皮肤和角膜中表达OPN 5的特定细胞, 表征它们的光反应,表征这些细胞用于传播光的机制, 信息,并表征这些组织显示的光响应的昼夜节律性质。使用 一种小鼠系,可以从其测量昼夜荧光素酶报告基因作为时钟的代表 基因表达,我们已经证明,皮肤和角膜的时钟可以同步, 光和这种昼夜光感受是由OPN 5调节。这位昼夜节律记者将习惯于 监测培养物中的组织,以及仅在OPN 5中包含荧光蛋白的小鼠系 表达细胞将允许我们确定视网膜外感光细胞的精确身份。 最后,该提案试图将眼外光感受的表达与潜在的健康风险联系起来。 特别是皮肤,已经被证明有一天中最容易受到紫外线伤害的精确时间 皮肤癌和红斑的发展。本提案将审查业务方案5在以下方面发挥的作用: 控制细胞分裂的时间,对紫外线的急性反应,发育过程中的敏感性, 皮肤和角膜的全球转录格局。通过分析组织的分子状态 在一天中的不同时间暴露在特定的光照条件下,我们将更好地了解 我们将开始了解哺乳动物细胞科普高能光的方式, OPN 5来调节生物钟,以预测环境中的光变化。

项目成果

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Ethan D Buhr其他文献

Ethan D Buhr的其他文献

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{{ truncateString('Ethan D Buhr', 18)}}的其他基金

The role of OPN5 in extraocular circadian photoentrainment in mammals
OPN5 在哺乳动物眼外昼夜光诱导中的作用
  • 批准号:
    10246879
  • 财政年份:
    2017
  • 资助金额:
    $ 37.07万
  • 项目类别:
The role of OPN5 in extraocular circadian photoentrainment in mammals
OPN5 在哺乳动物眼外昼夜光诱导中的作用
  • 批准号:
    9361579
  • 财政年份:
    2017
  • 资助金额:
    $ 37.07万
  • 项目类别:
The identity and the functional properties of the retinal circadian clock.
视网膜生物钟的身份和功能特性。
  • 批准号:
    8253594
  • 财政年份:
    2012
  • 资助金额:
    $ 37.07万
  • 项目类别:
The identity and the functional properties of the retinal circadian clock.
视网膜生物钟的身份和功能特性。
  • 批准号:
    8423081
  • 财政年份:
    2012
  • 资助金额:
    $ 37.07万
  • 项目类别:

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