Properties of photoreceptors and Muller cells investigated with AO-OCT

使用 AO-OCT 研究光感受器和 Muller 细胞的特性

• 批准号: 9195103
• 负责人: Ravi S. Jonnal
• 金额: $ 9.78万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9195103
• 关键词: Affect; Anatomy; Award; Cell physiology; Cells; Cellular Morphology; Cellular Structures; Classification; Clinical; Computer Analysis; Computing Methodologies; Cone; Custom; Data; Dependence; Diagnosis; Dimensions; Disease; Electrophysiology (science); Electroretinography; Exhibits; Eye diseases; Fluorescein; Grant; Human; Image; Individual; Individual Differences; International; Kinetics; Knowledge; Laboratories; Lateral; Learning; Light; Link; Measures; Membrane; Mentors; Methods; Microscopic; Modification; Morphology; Mosaicism; Muller' s cell; Ophthalmology; Optical Coherence Tomography; Optical Methods; Optics; Phase; Photoreceptors; Play; Predisposition; Property; Psychophysics; Recovery; Research; Resolution; Retina; Retinal; Retinal Diseases; Role; Scanning; Scientist; Source; Stimulus; Structure; System; Techniques; Testing; Three-Dimensional Imaging; Time; Training; Uncertainty; Vertebrate Photoreceptors; Vision; Work; Writing; adaptive optics; base; career; clinical development; clinical imaging; experience; eye center; imaging system; instrumentation; interest; novel; optical fiber; public health relevance; response; retinal rods; three dimensional structure; tool; translational impact; vision science

DESCRIPTION (provided by applicant): The research proposed for this award will examine functional and structural properties of single cells in the human retina. The three Aims will link the candidate's scientific background and career plans to study the human retina using a combination of adaptive optics (AO) and optical coherence tomography (OCT) which provide high lateral and high axial resolution, respectively (~2.5 μm in all three dimensions). Aim 1 will use AO-OCT to determine how the microscopic structure of the photoreceptors gives rise to the bands of the outer retina visible in routine clinical images-bands whose anatomical origins are not known precisely. It will test the hypothesis about whether the third band is from multiple reflectors in the interdigitation zone of the RPE or the tips of individual photoreceptors. Aim 1 will also test hypotheses about the contributions of rods and S-cones to the OCT image. Aim 2 will exploit this knowledge to noninvasively measure function in single photoreceptors, and identify a subset of cones, putative S-cones, often thought to be the first cone type to be affected by outer retinal disease. Aim 3 will study the optical properties of the Müller cells which are known to sustain retinal cells, and have been proposed, controversially, to also act as optical fibers for guiding light to the photoreceptors. This Aim will test ideas about Müller cell wave-guiding properties, for the first time, in the living retina. The optical signatures of all of the retinal layers studied in each of the three Aims are seen in clinical OCT images, but their cellular origins are uncertain. The proposed research will thus provide data fundamental to understanding retinal structure and function, and will enrich our understanding of clinical OCT images of retinal disease. During the mentored phase of this Award, the candidate will draw on all phases of his previous vision science experience including adaptive optics and computational analysis of the 3D structure of retinal images, and will expand this experience in significant ways needed for his career plans. This work will be conducted in the laboratory of John S. Werner where AO-OCT instrumentation has been pioneered and conveniently located in the UC Davis Eye Center. One AO-OCT system is available for the candidate's modification and exclusive use. Training will be buttressed by mentoring and didactic courses with advisors, Edward N. Pugh, Jr. and Lawrence S. Morse, who are internationally renowned basic and clinical vision scientists, respectively. Additional didactic components include a 'Fluorescein' course normally taken by residents and fellows in Ophthalmology and a grant-writing course. The training provided through this K99 will set the stage for the candidate's independent career in vision science research.

描述（由申请人提供）：该奖项提议的研究将检查人类视网膜中单细胞的功能和结构特性。这三个目标将把候选人的科学背景和职业计划联系起来，利用自适应光学 (AO) 和光学相干断层扫描 (OCT) 的组合来研究人类视网膜，这两种技术分别提供高横向和高轴向分辨率（所有三个维度均约为 2.5 μm）。目标 1 将使用 AO-OCT 来确定光感受器的微观结构如何产生常规临床图像中可见的外视网膜带，其解剖起源尚不清楚。它将检验第三条带是否来自 RPE 交叉区域中的多个反射器或单个感光器尖端的假设。目标 1 还将测试有关视杆细胞和 S 视锥细胞对 OCT 图像的贡献的假设。目标 2 将利用这些知识来非侵入性地测量单个光感受器的功能，并识别视锥细胞的子集，即假定的 S 视锥细胞，通常被认为是第一个受外视网膜疾病影响的视锥细胞类型。目标 3 将研究穆勒细胞的光学特性，穆勒细胞已知可维持视网膜细胞的功能，并且有争议地被提议也可充当将光引导至感光器的光纤。该目标将测试有关穆勒池的想法 活体视网膜首次具有波导特性。这三个目标中每个目标所研究的所有视网膜层的光学特征都可以在临床 OCT 图像中看到，但它们的细胞起源尚不确定。因此，拟议的研究将为理解视网膜结构和功能提供基础数据，并将丰富我们对视网膜疾病临床 OCT 图像的理解。在该奖项的指导阶段，候选人将利用其先前视觉科学经验的所有阶段，包括自适应光学和视网膜图像 3D 结构的计算分析，并将以重大方式扩展这一经验 他的职业规划所需要的。这项工作将在 John S. Werner 的实验室中进行，该实验室率先使用了 AO-OCT 仪器，并且位于加州大学戴维斯分校眼科中心，交通便利。一套AO-OCT系统可供考生修改和专用。培训将得到导师爱德华·N·皮尤 (Edward N. Pugh, Jr.) 和劳伦斯·S·莫尔斯 (Lawrence S. Morse) 的指导和教学课程的支持，他们分别是国际知名的基础和临床视觉科学家。其他教学内容包括通常由眼科住院医师和研究员参加的“荧光素”课程以及资助写作课程。通过 K99 提供的培训将为候选人在视觉科学研究领域的独立职业生涯奠定基础。

项目成果

No evidence for loss of short-wavelength sensitive cone photoreceptors in normal ageing of the primate retina.

没有证据表明灵长类视网膜正常衰老过程中短波长敏感的视锥细胞会丧失。

• DOI: 10.1038/srep46346
• 发表时间: 2017
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Weinrich,TobiasW;Powner,MichaelB;Lynch,Aisling;Jonnal,RaviS;Werner,JohnS;Jeffery,Glen
• 通讯作者: Jeffery,Glen