A two-photon ophthalmoscope for human retinal imaging and functional testing

 描述（由申请人提供）：NEI大胆目标倡议在解决视觉系统成像（U 01）的技术需求和机会方面的既定目标之一是“开发用于与自然视觉相关的体内视网膜功能的非侵入性测量的新技术，包括在细胞水平和电活动的代谢可视化”。基于强大的新获得的初步数据，本申请提出了一种新仪器的开发，该仪器可以对视网膜进行非常详细的成像，与两种高度敏感的相关测试一起可用于评估视网膜功能。具体目标是：（A）使用小鼠双光子检眼镜（TPO），开发用于评估视觉的两个功能方面的新型诊断范例：类维生素A通过类维生素A循环的代谢流和视觉灵敏度。沿着质谱分析，我们将定义影响视网膜的图像、结构、功能和毒性分子之间的关键交叉点，并确定保护这种神经组织的潜在疗法; 和（B）开发和测试人类TPO成像和诊断工具。最初的测试将在替代猴/猪眼睛中进行，然后根据获得的知识，我们将对患有致盲视网膜疾病晚期的个体的眼睛进行成像。尽管这一提议"大胆“，但实际上可以在供资周期内完成。本文介绍了使该计划成功所需的科学问题和中期里程碑。

 DESCRIPTION (provided by applicant): One of the stated goals of the NEI Audacious Goal Initiative in addressing the technical needs and opportunities for imaging the visual system (U01) is "to develop new technology for the non-invasive measurement of retina function in vivo as related to natural vision, including visualization of metabolism at the cellular level and electrical activities". Based on strong newly acquired preliminary data, this application proposes the development of a new instrument that can image the retina in exceptional detail that together with two highly sensitive related tests can be used to evaluate retinal function. The specific aims are: (A) with a mouse two-photon ophthalmoscope (TPO), develop a novel diagnostic paradigm used to assess two functional aspects of vision: the metabolic flow of retinoids through the retinoid cycle and visual sensitivity. Along with mass spectrometric analyses, we will define critical intersections between images, structure, function and toxic molecules that affect the retina and identify potential therapies that preserve this neural tissue; and (B) develop and test a TPO imaging and diagnostic tool in humans. Initial tests will be done in a surrogate monkey/pig eye and then with the knowledge gained, we will image the eyes of individuals with advanced stages of blinding retinal diseases. Despite its' `audacity', this proposal can realistically be completed during the funding cycle. The scientific questions and interim milestones required to make this program successful are presented herein.