RUI: Pigment Granule Dispersion in Teleost Retinal Pigment Epithelium: Cholinergic Mechanisms

眼睛后面是视网膜，包括视网膜色素上皮(RPE)和感光细胞。许多脊椎动物的色素上皮细胞含有一种遮挡光线的暗色素，这种色素可以穿梭到RPE细胞的指状突起中，进而与光感受器交错。在硬骨鱼中，当眼睛处于明亮状态时，色素颗粒的分散是与光适应相关的视网膜反应的重要组成部分。目前还不完全清楚光感受器的光信号如何触发RPE来控制这种色素分散。已知的一种细胞外信使是氨基酸多巴胺，最近的数据表明，复合氨基甲酚也可以诱导硬骨鱼RPE中的色素颗粒分散。由于卡巴胆碱模仿神经递质乙酰胆碱的作用，卡巴胆碱效应的发现表明，乙酰胆碱作为一种生理信使分子向RPE发出强光信号。乙酰胆碱和卡巴胆碱通过与一类被称为M受体的分子受体结合来作用于靶细胞。该项目使用分子技术和目前从斑马鱼基因组项目中获得的信息来测试蓝鳍金枪鱼是否有表达特定类型的M受体的基因，以及这些受体是否对氨基甲胆碱诱导的扩散负责。研究结果将确定乙酰胆碱如何在硬骨鱼眼部RPE中作为细胞外信使，并将通过促进我们对毒碱受体和胆碱能信号生物学的理解，产生超出感觉神经生物学的影响。本科生机构研究(RUI)项目也为本科生培训提供了极好的机会，特别是包括来自历史上服务不足的少数族裔群体的学生，少数族裔女教员PI作为榜样。

At the back of the eye is the retina, which includes the retinal pigment epithelium (RPE) as well as photoreceptor cells. The cells of the pigment epithelium in many vertebrates contain a dark pigment that screens light, and this pigment can shuttle out into finger-like projections of the RPE cells htat in turn interdigitate with the photoreceptors. In teleost fish, when the eye is in bright conditions, pigment granule dispersion is an important component of retinal responses associated with light adaptation. It is not fully clear how a light signal to the photoreceptors triggers the RPE to control this pigment dispersion. One extracellular messenger is known to be the amino acid dopamine, and recent data show that the compound carbachol also induces pigment granule dispersion in teleost fish RPE. Because carbachol mimics the effects of the neurotransmitter acetylcholine, the discovery of carbachol's effects suggests a role for acetylcholine as a physiological messenger molecule signaling bright light conditions to the RPE. Acetylcholine and carbachol act on target cells by binding to a class of molecular receptors called muscarinic receptors. This project uses molecular techniques and information currently available from zebrafish genome projects to test whether bluegill fish have genes to express particular types of muscarinic receptors, and whether these receptors are responsible for the carbachol-induced dispersion. Results will establish how acetylcholine might act as an extracellular messenger in the teleost eye RPE, and will have an impact beyond sensory neurobiology by advancing our understanding of the biology of muscarinic receptors and cholinergic signaling. This Research at Undergraduate Institutions (RUI) project also provides an excellent opportunity for undergraduate training, in particular including students from historically underserved minority groups, with a minority woman faculty PI as a role model.