Optical Imaging of the Retina: A window on visual development and the aging brain

视网膜光学成像：视觉发育和大脑老化的窗口

• 批准号: RGPIN-2020-05240
• 负责人: Campbell, Melanie
• 金额: $ 2.99万
• 依托单位: University of Waterloo
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=740472
• 关键词: Optical; Imaging; Retina; window; visual

My team and I will apply unique imaging techniques to give important insights into early eye development and aging of the eye and brain. Long term aims are 1) to develop novel optical corrections to slow progressive near-sightedness, a sight threatening condition with a rapidly increasing prevalence; 2) via novel imaging of proteins near retinal nerve cells in the eye, achieve diagnostic prediction of protein loads in the brain which are associated with diseases of aging. Inventions will be patented and commercialized with economic and health benefits to Canadians. Lab members will study the image across the back of the growing eye and signals for 1) when the image is focused and 2) the direction of image defocus. We will measure the ability of light activated cells to resolve these signals. Then we will compare signals and resolution in chick and children's eyes, including those which have grown in focus, are at risk of growing out of focus and those that require correction for defocus. From the differences in optical signals and image resolution between groups, we will design innovative optical corrections that could provide missing optical signals and reduce the incidence of near-sightedness. In the older eye, in tissue, our study will determine if novel, dye-free imaging of retinal deposits of proteins tau and alpha synuclein predicts changes in protein loads in the brain as we previously found for amyloid protein. Positive predictions will confirm that retinal deposits are novel markers of multiple common brain diseases. We will build, modify and test a unique retinal imaging instrument to quantify retinal deposits in a few eyes for each of the proteins. Smaller proteins in retinal tissue will also be imaged as they cause initial neural damage. The resulting less expensive instrument will have many advantages over brain scans. It will allow for earlier prediction and tracking of risks of neural damage with age in the brain and more precise diagnosis of neurodegenerative diseases. It will enable earlier, cheaper, targeted therapies aimed at reducing protein loads in the aging brain prior to the development of associated diseases. Novel diagnostic instruments will be commercialized, improving quality of life and reducing the societal burden of neurodegeneration. 17 HQP (11 graduate students, 5 undergrads and 1 research assistant) will gain a comprehensive understanding of imaging, including various microscopies and eye imaging, as well as instrument design, construction and testing. They will benefit from exposure to vision science, neuroscience, photonics and biophysics. Exposure will range from fundamental understanding of the eye's image and the cells that sample it, protein deposit morphology and image properties to the process of patenting and commercializing inventions. Trainees will gain broad experience working with collaborators and industry partners. Their skills and experience are in demand, for example by biophotonics companies.

我和我的团队将应用独特的成像技术，对眼睛的早期发育以及眼睛和大脑的衰老提供重要的见解。长期目标是：1）开发新的光学矫正，以减缓渐进性近视，这是一种患病率迅速增加的视力威胁状况; 2）通过对眼睛视网膜神经细胞附近的蛋白质进行新的成像，实现对大脑中与衰老疾病相关的蛋白质负荷的诊断预测。发明将获得专利并商业化，为加拿大人带来经济和健康利益。实验室成员将研究生长中的眼睛后部的图像，并发出1）图像何时聚焦和2）图像散焦方向的信号。我们将测量光激活细胞分辨这些信号的能力。然后，我们将比较小鸡和儿童眼睛的信号和分辨率，包括那些已经生长在焦点上的眼睛，那些有失去焦点的风险的眼睛，以及那些需要校正散焦的眼睛。根据各组之间光学信号和图像分辨率的差异，我们将设计创新的光学矫正，可以提供丢失的光学信号，减少近视的发生率。在老年人的眼睛中，在组织中，我们的研究将确定蛋白质tau和α突触核蛋白的视网膜沉积物的新型无染料成像是否可以预测大脑中蛋白质负荷的变化，就像我们以前发现的淀粉样蛋白一样。积极的预测将证实视网膜沉积物是多种常见脑部疾病的新标志物。我们将建立，修改和测试一个独特的视网膜成像仪器，以量化视网膜沉积在几只眼睛的每一种蛋白质。视网膜组织中较小的蛋白质也将被成像，因为它们会导致最初的神经损伤。由此产生的更便宜的仪器将比大脑扫描有许多优势。它将允许更早地预测和跟踪大脑中神经损伤的风险，并更精确地诊断神经退行性疾病。它将使更早，更便宜，有针对性的治疗，旨在减少相关疾病发展之前衰老大脑中的蛋白质负荷。新的诊断仪器将商业化，提高生活质量，减少神经退行性疾病的社会负担。17名HQP（11名研究生，5名本科生和1名研究助理）将全面了解成像，包括各种显微镜和眼睛成像，以及仪器设计，建造和测试。他们将受益于接触视觉科学，神经科学，光子学和生物物理学。接触的范围将从眼睛的图像和采样它的细胞，蛋白质存款形态和图像属性的专利和商业化发明的过程的基本理解。学员将获得与合作者和行业合作伙伴合作的广泛经验。他们的技能和经验很受欢迎，例如生物光子公司。