Advanced Technology to Study Visual Function on a Cellular Scale

描述（由申请人提供）：该项目是开发和支持三个国家的最先进的光学仪器，提供显微镜访问活视网膜，并使用它们来获得更清楚地了解人类视觉系统如何工作。他们将被用来回答有关视网膜中最重要和最具挑战性的区域的问题，中央凹。这些仪器建立在两个关键技术优势之上-自适应光学扫描激光检眼镜（AOSLO）系统和精确、高速的眼球运动跟踪。自适应光学（AO）技术可以纠正眼睛的缺陷，并可用于生成活体视网膜的显微视图。AO还能够将超清晰图像传递到视网膜。眼动跟踪用于测量和补偿始终存在的眼动。总之，这些允许准确的可视化，跟踪和光传递到视网膜 它具有像单锥感光器一样小的特征，能够以前所未有的规模测量空间和颜色视觉的特性。虽然这三个系统将是相同的，并将用于在细胞规模上测试视力，但每个系统的研究范围将非常不同。亚拉巴马大学伯明翰分校的AOSLO将用于测试灵长类动物的视力，加州大学伯克利分校的AOSLO将用于对健康人眼进行高级视力测试，加州大学弗朗西斯科分校的AOSLO将用于研究眼疾患者。让BRP管理三个相同的系统的主要优势是，它将促进硬件创新，以及从动物模型到临床的知识和创新测试的快速转化。目标1：在每个地点开发和部署最先进的AOSLO系统。通过在猴子和人类中进行客观的密度测定来展示性能，以绘制有助于色觉的三类锥状光感受器。目标2：在每个系统中开发改进的眼动跟踪和刺激传递能力。通过使用主观心理物理测试来映射与目标1中相同的三个类别的视锥光感受器来确认性能。目标3：在猴子和人类身上进行一系列实验，绘制视网膜和大脑内部和之间的连接和相互作用，并研究我们如何在眼睛不断运动的情况下看到稳定的世界。目标4：在临床中应用先进的视力测试方法，以发现不同疾病中视锥细胞死亡的机制，监测疾病进展过程中视锥细胞功能和结构的变化，并测试旨在阻止或减缓疾病进展的治疗效果。目标5：通过提供软件、硬件设计和论坛，让更多的受众能够使用眼动追踪和有针对性的刺激传递功能，让任何有兴趣构建类似先进系统的人都能使用这些功能。

DESCRIPTION (provided by applicant): This project is to develop and support three state-of-the-art optical instruments that provide microscopic access to the living retina, and use them to obtain a clearer understanding of how the human visual system works. They will be used to answer questions about the most important and the most challenging region in the retina to study, the fovea. The instruments are built upon two key technical strengths - adaptive optics scanning laser ophthalmoscope (AOSLO) systems and accurate, high-speed eye-motion tracking. Adaptive optics (AO) technology corrects the imperfections in the eye and can be used to generate microscopic views of the living retina. AO also enables the delivery of ultra-sharp images to the retina. Eye tracking is used to measure and compensate for ever-present eye motion. Together, these allow for accurate visualization, tracking and delivery of light to retinal features as small as single cone photoreceptors, enabling measurements of properties of spatial and color vision on an unprecedented scale. Although the three systems will be identical and will be used to test vision on a cellular scale, the scope of study for each system will be very different. The AOSLO at the University of Alabama, Birmingham will be used to test vision in primates, the AOSLO at the University of California, Berkeley will be used to perform advanced vision testing on healthy human eyes, and the AOSLO at the University of California, San Francisco will be used to study patients with eye disease. The key advantage of having the BRP manage three identical systems is that it will facilitate hardware innovations plus rapid translation of knowledge and innovative testing from animal models to the clinic. Briefly, the specific aims are: Aim 1: Develop and deploy state-of-the-art AOSLO systems at each site. Demonstrate performance by performing objective densitometry measures in monkeys and humans to map the three classes of cone photoreceptor that subserve color vision. Aim 2: Develop improved eye tracking and stimulus delivery capabilities in each system. Confirm performance by using subjective psychophysical tests to map the same three classes of cone photoreceptor as in Aim 1. Aim 3: Perform a series of experiments in monkeys and humans to map the connections and interactions within and between the retina and the brain and to study how we see the world as stable even though our eyes are in constant motion. Aim 4: Apply advanced vision testing methods in the clinic to discover mechanisms for cone death in different diseases, to monitor changes in cone function and structure during disease progression and to test the efficacy of treatments that aim to stop or slow disease progression. Aim 5: Make eye tracking and targeted stimulus delivery capabilities accessible to a wider audience by providing software, hardware designs and a forum for anyone interesting in building similar advanced systems.