Properties of photoreceptors and Muller cells investigated with AO-OCT

 描述(由申请人提供)：该奖项建议的研究将检查人类视网膜中单个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规划联系起来，使用自适应光学(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(三个维度均为~2.5μm)。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部视网膜带-其解剖来源尚不清楚。它将检验关于第三个波段是来自RPE交叉区的多个反射器还是来自单个光感受器尖端的假设。目标一号还将测试有关视杆和S视锥对OCT图像的贡献的假设。目的2将利用这一知识来非侵入性地测量单个光感受器的功能，并鉴定视锥细胞的一个子集，推测为S视锥细胞，通常被认为是第一个受到视网膜外部疾病影响的视锥细胞类型。目的3将研究米勒细胞的光学性质，已知的是维持视网膜细胞，并已被提出，有争议的，也作为光纤引导光到光感受器。这一目标将检验关于Müler cell的想法 第一次，在活的视网膜中具有波导性。在临床OCT图像中可以看到在三个目标中研究的所有视网膜层的光学特征，但它们的细胞来源尚不确定。因此，该研究将为了解视网膜的结构和功能提供基础数据，并将丰富我们对视网膜疾病的临床OCT图像的理解。在这个奖项的指导阶段，候选人将利用他以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，并将以重要的方式扩展这一经验 是他职业生涯规划所需要的。这项工作将在约翰·S·沃纳的实验室进行，这里是位于加州大学戴维斯分校眼科中心的AO-OCT仪器的先驱和便利的位置。一套AO-OCT系统可供考生修改和独家使用。培训将通过导师和指导课程得到支持，小爱德华·N·普格(Edward N.Pugh，Jr.)和劳伦斯·S·莫尔斯，他们分别是国际知名的基础和临床视觉科学家。其他教学内容包括眼科住院医师和研究员通常参加的“荧光素”课程，以及拨款撰写课程。通过K99提供的培训将为候选人在视觉科学研究方面的独立职业生涯奠定基础。

 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 whih 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 ofthe retinal layers studied in each of the three Aims are seen in clinical OCT images, but their cellula 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.