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

在眼睛的后部是视网膜，其包括视网膜色素上皮（RPE）以及感光细胞。许多脊椎动物的色素上皮细胞含有一种屏蔽光线的深色色素，这种色素可以穿梭到RPE细胞的指状突起中，进而与光感受器相互交错。在硬骨鱼中，当眼睛处于明亮条件下时，色素颗粒分散是与光适应相关的视网膜反应的重要组成部分。 目前尚不完全清楚到达光感受器的光信号如何触发RPE来控制这种色素分散。 已知一种细胞外信使是氨基酸多巴胺，并且最近的数据显示化合物卡巴胆碱也诱导硬骨鱼RPE中的色素颗粒分散。 由于卡巴胆碱模拟神经递质乙酰胆碱的作用，因此卡巴胆碱作用的发现表明乙酰胆碱作为生理信使分子向RPE发出明亮光条件的信号。 乙酰胆碱和卡巴胆碱通过与一类称为毒蕈碱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计划中获得的信息来测试蓝鳃鱼是否具有表达特定类型的毒蕈碱受体的基因，以及这些受体是否负责卡巴胆碱诱导的分散。 结果将确定乙酰胆碱如何可能作为细胞外信使在硬骨鱼眼RPE，并将有超越感觉神经生物学的影响，通过推进我们的生物学的毒蕈碱受体和胆碱能信号。 该研究在本科院校（RUI）项目还提供了一个很好的机会，本科培训，特别是包括学生从历史上服务不足的少数群体，与少数民族女教师PI作为一个榜样。

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.