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

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老化提供重要的见解。长期目标是1)开发新的光学矫正方法来治疗缓慢进行性近视，这是一种发病率迅速上升的威胁视力的疾病；2)通过对眼睛中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方面的好处。 实验室成员将研究不断增长的眼睛后部的图像，并发出1)图像何时对焦和2)图像散焦方向的信号。我们将测量光激活细胞解析这些信号的能力。然后我们将比较小鸡和儿童眼睛中的信号和分辨率，包括那些已经长出焦点的眼睛，面临着成长过程中焦点模糊的风险，以及那些需要纠正散焦的眼睛。根据不同群体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校正，以提供缺失的光学信号，并减少近视的发生率。 在老年眼的组织中，我们的研究将确定是否像我们之前在淀粉样蛋白中发现的那样，对tau和α突触核蛋白的视网膜沉积进行新的、无染料的成像，预测大脑中蛋白质负荷的变化。积极的预测将证实视网膜沉积是多种常见脑部疾病的新标志。我们将建造、修改和测试一种独特的视网膜成像仪器，以量化每种蛋白质在几只眼睛中的视网膜沉积。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脑部扫描有许多优势。它将允许更早地预测和跟踪大脑中随年龄增长的神经损伤风险，并更准确地诊断神经退行性疾病。它将使更早、更便宜、更有针对性的治疗成为可能，目的是在相关疾病发生之前减少老化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，减轻神经变性的社会负担。 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。他们将受益于视觉科学、神经科学、光子学和生物物理学。曝光的范围从对眼睛图像和采样细胞的基本了解，蛋白质沉积形态和图像属性，到发明专利和商业化的过程。学员将获得与合作者和行业合作伙伴合作的广泛经验。例如，生物光子学公司需要他们的技能和经验。

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.