Functional imaging of retinal photoreceptors

视网膜感光器的功能成像

• 批准号: 9090114
• 负责人: XINCHENG YAO
• 金额: $ 33.9万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9090114
• 关键词: Affect; Age related macular degeneration; Alabama; Amphibia; Animal Model; Animals; Aspartate; Biological Markers; Blindness; Cell membrane; Cells; Characteristics; Clinical; Clinical Research; Defect; Dependence; Detection; Diabetic Retinopathy; Diagnosis; Disease; Drusen; Early Diagnosis; Electrophysiology (science); Evaluation; Eye diseases; Feedback; Functional Imaging; Functional disorder; Future; Glaucoma; Health; Histology; Hybrids; Image; Individual; Inherited; Laser Scanning Confocal Microscopy; Lasers; Lead; Legal Blindness; Light; Maps; Measurement; Medicare; Metabolic; Methods; Microscope; Microscopy; Mitochondria; Modeling; Modification; Morphology; Mus; Ophthalmoscopes; Optical Coherence Tomography; Optics; Pathway interactions; Patients; Phase; Photoreceptors; Physiologic Monitoring; Physiological; Physiology; Protocols documentation; Rana; Recovery; Resolution; Retina; Retinal; Retinal Cone; Retinal Diseases; Retinal Photoreceptors; Signal Transduction; Source; Stimulus; System; Testing; Time; Universities; Vertebrate Photoreceptors; Visual impairment; base; cell type; clinical application; clinically relevant; comparative; cost; histological studies; imaging modality; improved; in vivo; in vivo imaging; injured; mouse model; mutant; photoreceptor degeneration; response; retinal adaptation; retinal neuron; retinal rods; retinal stimulation; success; visual phototransduction

DESCRIPTION (provided by applicant): Many eye diseases, such as age-related macular degeneration (AMD), diabetic retinopathy (DR) and glaucoma, involve pathological changes in retinal photoreceptors and/or inner retinal neurons. It is well known that different diseases can target different cell types. In principle, physiological modification must occur in diseased cells, before detectable abnormality of retinal morphology. Therefore, functional evaluation of retinal physiology is important for early disease detection and reliable treatment management. At University of Alabama at Birmingham (UAB), we have developed several optical approaches, including functional optical coherence tomography (OCT) and line-scan confocal microscopy, to pursue optophysiological monitoring of physiological activities using transient intrinsic optical signal (IOS) changes correlated with retinal stimulation. We propose here to validate functional IOS mapping of photoreceptor physiology at high resolution (< 50 m). Success of this project can lead to better study and diagnosis of photoreceptor dysfunction associated with eye diseases, including AMD which is the leading cause of severe vision loss and legal blindness. Our preliminary study has revealed IOS abnormalities in one mouse model with inherited photoreceptor degeneration, and in vivo confocal-IOS observation of individual frog photoreceptors have been demonstrated. Fast confocal-IOS imaging promises a high-resolution method for functional examination of photoreceptor physiology, while simultaneously providing information of retinal morphology. However, before clinical deployments of the functional IOS imaging, there are several obstacles: 1) IOS mechanism in the retina is not clear; 2) IOS imaging protocol of rod and cone systems is not developed; 3) clinical relevance between IOS modification and retinal disease is not established. These problems will be tackled in our three specific aims of this project. The first aim is to investigate physiological sources of the IOS. A hybrid confocal-OCT microscope will be employed to dissect the IOS in the photoreceptor and inner retinal cells at sub-cellular resolution. Comparative measurement of normal and aspartate-treated retinas will be used to test physiological pathways of the IOS. The second aim is to develop stimulation protocol for functional IOS mapping of retinal photoreceptors. We anticipate that selective mapping of localized (e.g., 50 m) rod and cone functions can be achieved through quantitative controls of retinal adaptation and stimulation, without the requirement of resolving individual photoreceptors. The third aim is to establish clinical potential of functional IOS imaging. One inherited photoreceptor degeneration model rd10, i.e., C57BL/6J-Pde6brd10, will be used for comparative IOS, electrophysiological, and histological study. Success criterion of this study is to demonstrate that the IOS imaging allows early detection of photoreceptor dysfunction at the time point no later than detectable structural changes in the retina. By the end of this project, ultimate imaging modality (i.e., confocal or OCT) for clinical application will be identified based on quantitative comparison of confocal- and OCT-IOS images.

描述（由申请人提供）：许多眼科疾病，例如与年龄相关的黄斑变性（AMD），糖尿病性视网膜病（DR）和青光眼，涉及视网膜感光体和/或视网膜内神经元的病理变化。众所周知，不同的疾病可以针对不同的细胞类型。原则上，生理修饰必须发生在患病的细胞中， 在可检测到视网膜形态的异常之前。因此，视网膜生理的功能评估对于早期疾病检测和可靠的治疗管理很重要。在伯明翰大学（UAB）的阿拉巴马大学，我们开发了几种光学方法，包括功能性光学相干断层扫描（OCT）和线扫描共聚焦显微镜，以使用短暂的固有光学信号（ios）改变与护理刺激相关的瞬态光学信号（IOS）对生理活性进行选择性监测。我们在这里建议以高分辨率（<50 m）验证光感受器生理的功能iOS映射。该项目的成功可能会导致对与眼病相关的感光体功能障碍的更好研究和诊断，包括AMD，这是严重视力丧失和法律失明的主要原因。我们的初步研究揭示了一种具有遗传感受器变性的小鼠模型中的iOS异常，并且已经证明了单个青蛙光感受器的体内共聚焦-IOS观察。快速共聚焦IOS成像有望使用光感受器生理功能检查的高分辨率方法，同时提供视网膜形态的信息。但是，在功能性iOS成像的临床部署之前，有几个障碍：1）视网膜中的iOS机制尚不清楚； 2）杆和锥体系统的iOS成像协议未开发； 3）未建立iOS修饰与视网膜疾病之间的临床相关性。这些问题将在我们该项目的三个具体目标中解决。第一个目的是研究iOS的生理来源。将采用杂交共聚焦显微镜以亚细胞分辨率在感光体和内部视网膜细胞中剖析iOS。正常和天冬氨酸处理的视网膜的比较测量将用于测试iOS的生理途径。第二个目的是为视网膜光感受器的功能iOS映射开发刺激方案。我们预计，可以通过定量控制视网膜适应和刺激来实现局部（例如50 m）杆和锥函数的选择性映射，而无需解决单个光感受器。第三个目的是建立功能性iOS成像的临床潜力。一种遗传的光感受器变性模型RD10，即C57BL/6J-PDE6BRD10，将用于比较iOS，电生理学和组织学研究。这项研究的成功标准是证明iOS成像允许在时间点早期检测到光感受器功能障碍，而不是视网膜中可检测的结构变化。到最后 在这个项目中，将用于临床应用的最终成像方式（即共聚焦或OCT） 根据共聚焦和OCT-IOS图像的定量比较确定。