Platform Technologies for Microscopic Retinal Imaging: Development & Translation

显微视网膜成像平台技术：开发

基本信息

批准号：
9059095
负责人：
Joseph Carroll
金额：
$ 86.67万
依托单位：
MEDICAL COLLEGE OF WISCONSIN
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2016-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9059095
关键词：
Address Animal Model Animals Biological Markers Cell physiology Cells Cellular Structures Clinical Clinical Trials Computer software Computers Cone Degenerative Disorder Detection Development Diagnosis Disease Ear Ensure Eye Eye diseases Financial compensation Fluorescence Resonance Energy Transfer Future Genes Goals Grant Health Human Image Imagery Imaging Device Imaging technology Individual Institution Interdisciplinary Study Intervention Intraocular lens implant device Life Lighting Location London Mechanics Methods Microscopic Monitor Motion Natural regeneration Neurons New York Ophthalmoscopes Ophthalmoscopy Optics Outcome Pathogenesis Pathologic Nystagmus Patients Pennsylvania Performance Phase Photons Photoreceptors Physiological Population Property Psychophysics Pupil Replacement Therapy Resolution Retina Retinal Retinal Degeneration Retinal Diseases Retinal Ganglion Cells Rodent Sampling Scanning Scientist Site Stimulus Structure Techniques Technology Testing Therapeutic Therapeutic Intervention Time Translations Universities Vision Visual system structure Wisconsin Work adaptive optics cell type cellular imaging college experience fluorescence imaging ganglion cell gene replacement therapy image registration imaging modality improved in vivo information gathering insight lens medical schools new technology next generation non-invasive imaging novel patient population pre-clinical public health relevance regenerative therapy relating to nervous system response technology development tool two-photon

项目摘要

DESCRIPTION (provided by applicant): Strategies for treating degenerative retinal diseases are evolving at a rapid pace; however there exist major gaps impeding progress towards the ultimate audacious goal of regenerating neurons in the eye to restore sight. Technologies for monitoring the presence and health of individual photoreceptors and ganglion cells in living animal and human retinae are desperately needed. These tools would provide critical insight into the pathogenesis of a number of retinal and neuro-degenerative diseases; such insight is a requisite first step to developing the appropriate therapeutic approaches for a given patient/disease. Furthermore, improved visualization of cellular structure and function in patients with retinal degenerative diseases will permit scientists and clinicians to more precisely target and monitor the outcome of their therapeutic interventions. We have assembled a multidisciplinary research team uniquely equipped to address this major technological need. Drawing on our extensive experience in developing adaptive optics and retinal imaging tools, we propose to develop and disseminate four complementary platform/enabling technologies. We will leverage our existing collaborative relationships among all five participating sites, synergisic expertise, and access to extensive animal models along with an unrivaled patient population for testing these technologies. The specific technologies we propose to develop are: 1) Real-time retinal motion compensation, allowing retinal cellular-resolution imaging even in cases of extreme involuntary eye motion, like nystagmus; 2) Adaptive longitudinal chromatic aberration correction, allowing multi-wavelength, cellular-resolution retinal imaging; 3) Super- resolution line scanning ophthalmoscopy, to non-invasively image previously inaccessible cells and provide the largest image resolution improvement (> 50%) since the original demonstration of ophthalmic adaptive optics; and 4) High-throughput, opto-physiological method for assessing photoreceptor function with cellular resolution, providing a sensitive biomarker for assessing the function of regenerated/restored cells. A major strength of this application is that through our collaborative network we will validate the utility of these new technologies using regenerative therapies in both pre-clinical and clinical settings. This work will have a significant positive impact by enabling diagnosis of retinal disease and monitoring of retinal structure and function with unprecedented sensitivity and resolution. Finally, the focus of the proposed technologies will be photoreceptor and retinal ganglion cell imaging to explicitly advance the audacious goal, but they will not be limited to assessing any one therapeutic approach or cell type. Rather they will be generalizable and broadly applicable to all retinal cell types, retinal diseases, and therapeutic strategies.

描述（由申请人提供）：治疗退行性视网膜疾病的策略正在快速发展；然而，在实现眼睛再生神经元以恢复视力的技术这一大胆目标方面仍存在重大差距。迫切需要活体动物和人类视网膜中的单个光感受器和神经节细胞，这些工具将为许多视网膜和神经退行性疾病的发病机制提供重要的见解；为特定患者/疾病开发适当的治疗方法的必要的第一步此外，改善患者细胞结构和功能的可视化。视网膜退行性疾病的研究将使科学家和指挥官能够更精确地瞄准和监测其治疗干预的结果，我们已经组建了一个独特的多学科研究团队，可以利用我们在开发自适应光学和视网膜成像方面的丰富经验。工具，我们建议开发和传播四种互补的平台/支持技术，我们将利用所有五个参与地点之间现有的合作关系、协同专业知识以及广泛的动物模型和无与伦比的患者群体来测试这些技术。我们建议开发的具体技术是：1）实时视网膜运动补偿，即使在眼球震颤等极端非自愿眼球运动的情况下也可以进行视网膜细胞分辨率成像；2）自适应纵向色差校正，允许多波长、细胞- 分辨率视网膜成像；3）超分辨率线扫描检眼镜，以非侵入性方式对以前无法接近的细胞进行成像，并提供自有史以来最大的图像分辨率改进（> 50%）眼科自适应光学的原始演示；以及 4) 用于以细胞分辨率评估光感受器功能的高通量光生理学方法，为评估再生/恢复细胞的功能提供敏感的生物标记。通过合作网络，我们将在临床前和临床环境中使用再生疗法来验证这些新技术的实用性，这项工作将以前所未有的方式诊断视网膜疾病并监测视网膜结构和功能，从而产生重大的积极影响。最后，拟议技术的重点将是光感受器和视网膜神经节细胞成像，以明确推进这一大胆的目标，但它们不会仅限于评估任何一种治疗方法或细胞类型，而是具有普遍性和广泛性。适用于所有视网膜细胞类型、视网膜疾病和治疗策略。