Functions of OPN5 and OPN3 in the eye

OPN5 和 OPN3 在眼睛中的功能

• 批准号: 9380871
• 负责人: Russell N. Van Gelder
• 金额: $ 48万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9380871
• 关键词: Affect; Anatomy; Animals; Cells; Circadian Rhythms; Cornea; Darkness; Data; Diffuse; Electrophysiology (science); Electroretinography; Eye; Functional disorder; Genes; Hour; Image; Impairment; Laboratories; Life; Light; Malignant Neoplasms; Mental disorders; Morphology; Nature; Neurotransmitters; Opsin; Orphan; Periodicity; Pharmacology; Photophobia; Photoreceptors; Photosensitivity; Phototransduction; Physiology; Process; Pupil light reflex; Retina; Retinal; Retinal Ganglion Cells; Signal Transduction; Sleep Disorders; System; Techniques; Tissues; Transgenic Animals; Vertebrate Photoreceptors; Visual; Work; circadian pacemaker; experimental study; genetic analysis; insight; knockout animal; melanopsin; novel; patch clamp; response; suprachiasmatic nucleus; tool

PROJECT SUMMARY/ABSTRACT Circadian rhythms are the near-24-hour rhythms of physiology ubiquitous to almost all eukaryotic life. Dysfunction of circadian rhythms underlies a variety of common sleep disorders and is thought to contribute to other conditions ranging from psychiatric disease to cancer. The mammalian retina serves a critical function in synchronizing the master circadian pacemaker (the suprachiasmatic nucleus) to the daily light-dark cycle. Work over many years has also demonstrated that the retina itself is a strong circadian oscillator. Indeed, many critical retinal functions, including visual sensitivity, the pupillary light reflex, the electroretinogram, and the expression of hundreds of retinal genes, are under strong circadian control; and that loss of retinal circadian rhythms results in impaired retinal function. Our preliminary data have demonstrated that: 1) the retinal circadian clock can be entrained to light- dark cycles in culture ex vivo, 2) this entrainment is not dependent on the classical rods and cones or the melanopsin-expressing, intrinsically-photosensitive retinal ganglion cells, 3) the orphan opsin neuropsin (OPN5) is necessary for this photoentrainment, and the orphan opsin encephalopsin (OPN3) affects this process, 4) the retina utilizes a light-dependent, diffusible substance to synchronize its rhythms, and 5) the cornea also contains a circadian clock which, remarkably, can be entrained to light- dark cycles as well via an OPN5-dependent mechanism. We propose experiments to elucidate the signaling mechanisms of OPN5 and OPN3; experiments to characterize the diffusible signal(s) emanating from the retina, and experiments to elucidate the mechanism by which non-retinal tissues in the eye maintain circadian rhythmicity and entrain to light-dark cycles. These data will provide a critical basis for understanding how the circadian clock modulates retinal function as well as mechanistic insights into two novel ocular photoreceptors.

项目摘要/摘要 昼夜节律是生理学的接近24小时的节奏，几乎无处不在 真核生物生活。昼夜节律的功能障碍是各种常见的睡眠障碍的基础 被认为有助于其他疾病，从精神病到癌症。哺乳动物 视网膜在同步昼夜节奏起搏器方面发挥着关键作用 核）到每日浅黑暗周期。多年来的工作也表明了视网膜本身 是强大的昼夜振荡器。实际上，许多关键的视网膜功能，包括视觉敏感性， 瞳孔光反射，电视图和数百个视网膜基因的表达在 强大的昼夜节律；视网膜昼夜节律的丧失导致视网膜功能受损。 我们的初步数据表明：1）视网膜昼夜节律时钟可能被夹在光中 培养物中的黑暗周期，2）此夹带不取决于经典的棒和锥或 表达黑色素，本质上敏感的视网膜神经节细胞，3）孤儿蛋白 Neuropsin（OPN5）对于此光座是必需的，而孤儿Opsin脑奏素（OPN3）是必不可少的 影响这一过程，4）视网膜利用光依赖性的，可扩散的物质同步 节奏和5）角膜还包含一个昼夜节律时钟，显着地可以夹在光中 暗循环也通过OPN5依赖性机制。我们提出了实验以阐明 OPN5和OPN3的信号传导机制；表征可扩散信号的实验（S） 从视网膜发出，并进行实验，以阐明非视网膜组织中的机制 眼睛保持昼夜节律，并夹在浅黑暗周期中。这些数据将提供关键 了解昼夜节律如何调节视网膜功能和机械的基础 洞悉两个新型的眼镜感受器。