Anatomical and Biochemical Organization of the Retina

视网膜的解剖和生化组织

• 批准号: 7658714
• 负责人: JOHN E DOWLING
• 金额: $ 33.6万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7658714
• 关键词: Adult; Affect; Animals; Biochemical; Biological Models; Cells; Chemicals; Development; Disease; Electron Microscopy; Electrons; Electrophysiology (science); Electroretinography; Eye; Eye Development; Gene Expression; Gene Mutation; Genes; Glaucoma; Grant; Green Fluorescent Proteins; Immunohistochemistry; In Situ Hybridization; Individual; Inherited; Laboratories; Larva; Lazy Eyes; Light; Maps; Measures; Methodology; Methods; Microarray Analysis; Microscopic; Modeling; Mutagenesis; Mutate; Mutation; Observational Study; Physiologic Intraocular Pressure; Postdoctoral Fellow; Principal Investigator; Process; RNA; Research Design; Research Personnel; Retina; Retinal; Retinal Cone; Staining method; Stains; Structure; Techniques; Transgenic Organisms; Vision; Visual system structure; Zebrafish; behavior test; cell type; ganglion cell; gene cloning; graduate student; horizontal cell; knock-down; lens; mutant; programs; response; retinal rods; tool

DESCRIPTION (provided by applicant): The zebrafish is an ideal model system in which to study the effects of genetic mutations on eye development and function. Its retina contains four types of cones as well as abundant rods, and the animals are highly responsive visually, enabling the analysis of visual function by behavioral testing. Electrophysiological recordings from the eyes can also readily be made as well. This project is concerned with the isolation and analysis of visual system mutants induced in zebrafish by chemical mutagenesis techniques. Both recessive and dominant mutations have been induced that affect not only retinal function and development, but also lens development. In addition, a mutant has been isolated that is a model for glaucoma. These mutants, then, provide information not only about basic development and function of various eye structures, but they also provide models of various inherited diseases. Over the next four years, additional mutants that affect the eye will be sought. In addition, further analysis of already identified mutants will continue or be undertaken. The discovery of new mutants is accomplished by observational studies or by behavioral testing. Analyses of mutants include light and electron microscopic studies, immunohistochemistry, in situ hybridization and electrophysiology. In addition, gene expression studies using microarray analysis are carried out in certain cases as well as gene knock-down studies using morpholinos. The project will also seek to develop or adapt additional techniques to zebrafish for the analysis of visual system mutants. So, for example, methodology was developed over the past grant period to measure intraocular pressure in the eyes of zebrafish as well as for the staining of individual cell types (rods) using green fluorescent protein (GFP) and transgenic techniques. In the coming grant period, methodology for recording single cell electrical activity will be further developed, as well as techniques for identifying by, electron microscopy, processes from specific retinal cell types including horizontal cells.

描述（由申请人提供）：斑马鱼是研究基因突变对眼睛发育和功能影响的理想模型系统。它的视网膜包含四种视锥细胞和丰富的视杆细胞，动物的视觉反应非常灵敏，可以通过行为测试来分析视觉功能。眼睛的电生理记录也可以很容易地完成。本项目是通过化学诱变技术分离和分析斑马鱼的视觉系统突变体。隐性和显性突变不仅影响视网膜功能和发育，而且影响晶状体发育。此外，已经分离出一种突变体，它是青光眼的模型。因此，这些突变体不仅提供了有关各种眼睛结构的基本发育和功能的信息，而且还提供了各种遗传疾病的模型。