Platform Technologies for Microscopic Retinal Imaging: Development & Translation

显微视网膜成像平台技术：开发

• 批准号: 8912125
• 负责人: Joseph Carroll
• 金额: $ 92.74万
• 依托单位: MEDICAL COLLEGE OF WISCONSIN
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-05-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8912125
• 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

 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（适用提供）：治疗退化性残留疾病的策略正在快速发展；然而，存在主要的差距，阻碍了朝着恢复视力再生神经元的最终大胆目标。迫切需要监测生物和人类视网膜中个体感光细胞和神经节细胞的存在和健康的技术。这些工具将为许多视网膜和神经变性疾病的发病机理提供批判性的洞察力；这种洞察力是开发给定患者/疾病的适当治疗方法的必要第一步。此外，改善了患者细胞结构和功能的可视化 使用视网膜退行性疾病将使科学家和临床医生更精确地靶向和监测其治疗性干预措施的结果。我们已经组建了一个具有唯一等效的多学科研究团队，以满足这一主要技术需求。利用我们在开发自适应光学和视网膜成像工具方面的丰富经验，我们建议开发和传播四个完整的平台/启用技术。我们将利用所有五个参与网站，协同专业知识以及获得广泛的动物模型以及无与伦比的患者人群的现有协作关系来测试这些技术。我们建议开发的特定技术是：1）实时视网膜运动补偿，即使在像眼球震颤这样的极端非自愿性眼运动的情况下，也允许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）超分辨率线扫描眼镜检查，以前是非侵入性图像先前无法接近的细胞，并提供最大的图像分辨率改进（> 50％），因为眼科适应性光学的原始演示； 4）用于评估细胞分辨率的光感受器功能的高通量的光学生理方法，为评估再生/还原细胞的功能提供了灵敏的生物标志物。该应用程序的一个主要优势是，通过我们的协作网络，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。这项工作将通过实现视网膜疾病的诊断，并以前所未有的灵敏度和分辨率来监测视网膜结构和功能，从而产生重大的积极影响。最后，所提出的技术的重点将是光感受器和视网膜神经节细胞成像，以明确促进大胆的目标，但它们不限于评估任何一种治疗方法或细胞类型。相反，它们将是可推广的，并且广泛适用于所有常规细胞类型，永久性疾病和治疗策略。