Melatonin Signaling in Photoreceptors

光感受器中的褪黑激素信号传导

• 批准号: 10567523
• 负责人: Gianluca Tosini
• 金额: $ 5.71万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10567523
• 关键词: Affect; Age related macular degeneration; Aging; Apoptosis; Binding; Biological; Consumption; Data; Development; Diabetes Mellitus; Diet; Disease; Epidemic; Eye; Fatty acid glycerol esters; Food; G-Protein-Coupled Receptors; Genetic; Genetic Recombination; Goals; Health; High Fat Diet; Hormones; Human; Knockout Mice; Lead; Melatonin; Melatonin Receptors; Mus; Names; Neuromodulator; Obesity; Oxidative Stress; Pathogenesis; Pathway interactions; Photoreceptors; Physiological; Physiology; Play; Production; Property; Regulation; Reporting; Research; Retina; Retinal Diseases; Retinal Photoreceptors; Risk; Rod; Role; Signal Pathway; Signal Transduction; Speed; Structure; Techniques; Transgenic Mice; Treatment Efficacy; Vertebrate Photoreceptors; congenic; design; efficacy testing; experimental study; fight against; insight; negative affect; novel therapeutics; receptor; tool; translational study

Melatonin is an important player in the regulation of many physiological functions within the body and within the retina. Several studies have shown that melatonin synthesis in the retina primarily occurs during the night and its levels are low during the day. Melatonin exerts its influence by binding to G protein-coupled receptors named melatonin receptor type 1 (MT1) and type 2 (MT2). MT1 and MT2 receptors activate a wide variety of signaling pathways and both receptors are present in the vertebrate photoreceptors where they may form MT1/MT2 heteromers (MT1/2h). Previous studies have also demonstrated that melatonin may play an important role in protecting photoreceptors from oxidative stress and can protect photoreceptors from apoptosis. Critically, melatonin signaling is involved in the modulation of photoreceptor functioning and viability during aging. Finally, new experimental evidence indicates that high fat diet (HFD) leads to a significant decrease in the amplitude of a- and b-wave of the scotopic ERGs in mice lacking MT1 signaling. The goal of this application is to elucidate the role of melatonin signaling plays in in the modulation of photoreceptor functioning and to determine if melatonin may represent a useful tool in the fight against retinal disorders. The present application comprises two specific aims. In specific aim 1 we will produce a rod specific MT1 knock out mice in a melatonin proficient genetic background. In specific aim 2 we will investigate the mechanism(s) by which MT1/2h signaling protects photoreceptor cells HFD. In our research, we will use a wide array of new and technologically advanced techniques as well as we will develop new lines of transgenic mice. Our proposal will provide important insights about the role of melatonin signaling in the modulation of photoreceptor health.

褪黑激素是调节体内许多生理功能的重要参与者， 在视网膜内。几项研究表明，褪黑激素的合成主要发生在视网膜 在夜间，它的水平在白天很低。褪黑激素通过与G 蛋白质偶联受体，称为1型褪黑激素受体（MT 1）和2型褪黑激素受体（MT 2）。mt 1和mt 2 受体激活各种各样的信号通路，两种受体都存在于 脊椎动物光感受器，其中它们可以形成MT 1/MT 2异聚体（MT 1/2 h）。先前的研究 还表明褪黑激素可能在保护光感受器免受 氧化应激，并可保护光感受器免于凋亡。重要的是，褪黑激素信号是 参与调节老化过程中的光感受器功能和活力。最后，新 实验证据表明，高脂饮食（HFD）导致 缺乏MT 1信号传导的小鼠中暗视ERG的a波和b波振幅。这个目标 目的是阐明褪黑素信号在光感受器调节中的作用 功能，并确定是否褪黑激素可能是一个有用的工具，在打击视网膜病变， 紊乱本申请包括两个具体目的。在具体目标1中，我们将生产 在褪黑激素熟练遗传背景中的杆特异性MT 1敲除小鼠。在具体目标2中， 将研究MT 1/2 h信号传导保护感光细胞HFD的机制。在我们 研究，我们将使用各种新的和技术先进的技术，以及我们将 开发新的转基因小鼠品系。我们的建议将提供重要的见解， 褪黑激素信号在光感受器健康调节中的作用。

项目成果

Blue-light-blocking Lenses in Eyeglasses: A Question of Timing.

• DOI: 10.1097/opx.0000000000001866
• 发表时间: 2022-03-01
• 期刊: Optometry and vision science : official publication of the American Academy of Optometry
• 作者: Tosini G