Regulation of eye development by an Opsin5-dopamine pathway

Opsin5-多巴胺通路调节眼睛发育

• 批准号: 9461543
• 负责人: P Michael Iuvone
• 金额: $ 47.54万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9461543
• 关键词: Acute; Address; Adult; Amacrine Cells; Behavior; Biology; Birds; Birth; Blood Vessels; Breeding; Cell physiology; Cells; Circadian Rhythms; Clinical; Collaborations; Data; Detection; Development; Dopamine; Dopamine Receptor; Encapsulated; Eye; Eye Development; Future; Genes; Genetic; Hypotension; Light; Lighting; Mammals; Methods; Mutant Strains Mice; Neuromodulator; Ocular Physiology; Opsin; Optics; Participant; Pathway interactions; Photosensitivity; Physiological; Premature Infant; Production; Proteins; Regulation; Retina; Retinal; Retinal Ganglion Cells; Retinopathy of Prematurity; Role; Sensory; Signal Transduction; Source; Stimulus; Structure; Suggestion; Tissues; Tyrosine 3-Monooxygenase; VEGFA gene; Vascular Diseases; Vascular Endothelial Cell; Vision; Visual system structure; Work; circadian pacemaker; clinically relevant; design; gain of function; high risk; insight; loss of function; melanopsin; receptor; response; retinal angiogenesis; tool; uptake; vessel regression

ABSTRACT   Regulation of eye development by an Opsin 5-dopamine pathway. Neuropsin (OPN5) is an atypical opsin that we show is expressed in retinal ganglion cells of the vertebrate retina (we call these ip5RGCs). OPN5 is known to respond to near-UV wavelengths and to photoentrain a retinal circadian clock. Beyond this, very little is known about the physiological function of neuropsin in any tissue. In this application we reveal that during development of the eye, an OPN5 response pathway regulates levels of the crucial neuromodulator dopamine (DA). DA is known to have several functions in the visual system but among them, the best characterized is its role in regulating the adaptive response to nighttime and daytime lighting. We also reveal that DA has an important role directly influencing vascular development within the eye. Preliminary data suggest that DA acts as a negative regulator of vascular responses to promote hyaloid vessel regression and suppress retinal angiogenesis. Thus, DA acts as a counter to VEGFA, a pro-vascular stimulus. Our preliminary findings suggest the central hypothesis: An OPN5-dopamine pathway regulates vascular development of the eye. Our hypothesis incorporates the dual suggestions that OPN5 regulates DA activity and that DA directly regulates vascular development in the eye. We propose three experimental Aims designed to address the relationship between neuropsin activity and DA production: Aim 1: To determine whether ip5RGCs form physical connections with dopaminergic amacrine cells. Aim 2: To assess whether OPN5 regulates dopamine acutely or via the retinal circadian clock. Aim 3: To determine the mechanism by which DA regulates vascular development in the eye. When complete, these analyses will provide important new insights on the role of neuropsin in the physiology of the visual system. This analysis is also clinically relevant because a DA-vascular pathway is probably the explanation for the association between DA treatment of premature infants (for hypotension) and the potentially blinding vascular overgrowth of severe retinopathy of prematurity.

抽象的   OPSIN 5-多巴胺途径对眼睛发育的调节。 Neuropsin（OPN5）是非典型的 我们显示的Opsin在脊椎动物视网膜的视网膜神经节细胞中表达（我们称这些IP5RGC）。 众所周知，OPN5会对近紫外的波长做出响应，并对光伦丁的视网膜昼夜节律响应。超过 这对任何组织中神经蛋白酶的身体功能知之甚少。 在此应用程序中，我们揭示了眼睛的发育，OPN5响应途径 调节至关重要的神经调节剂多巴胺（DA）的水平。 DA在 视觉系统，但其中最好的特征是它在调节适应性反应中的作用 夜间和白天照明。我们还揭示了DA具有直接影响血管的重要作用 眼中的发展。初步数据表明DA充当血管的负调节剂 促进透明血管回归并抑制视网膜血管生成的反应。那是DA充当 对抗Vegfa，一种促血管刺激。我们的初步发现提出了中心假设： OPN5多巴胺途径调节眼睛的血管发育。我们的假设包括 OPN5调节DA活性并直接调节血管发育的双重建议 眼睛。我们提出了三个旨在解决神经蛋白活动之间关系的实验目标 和DA生产：目标1：确定IP5RGC是否与多巴胺能形成物理连接 无小细胞。目标2：评估OPN5是急性调节多巴胺还是通过视网膜昼夜节律调节 钟。目标3：确定DA调节眼睛血管发育的机制。什么时候 这些分析将提供有关神经蛋白在生理学中的作用的重要新见解 视觉系统。该分析也与临床相关，因为DA-血管途径可能是 解释早产婴儿的DA治疗（低血压）与 潜在地盲目的血管过度生长，严重的早产性视网膜病变。