Adaptive optics imaging and micro-stimulation to yield in vivo single-cell biomarker of retinal function and dysfunction in the human retina.

自适应光学成像和微刺激可产生人类视网膜视网膜功能和功能障碍的体内单细胞生物标志物。

• 批准号: 399370883
• 负责人: Dr. Wolf Harmening
• 金额: --
• 依托单位: Universitäts-Augenklinik Bonn
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/399370883?language=en
• 关键词: Adaptive; optics; imaging; micro; stimulation

Current clinical retinal imaging and function testing in subjects suffering from degeneration of the neuro-retina is not sensitive enough to pick up small but significant physiological changes within time frames that would be feasible for evaluation of emerging gene and cell based intervention efforts. We aim to close this gap with recently developed imaging and stimulation technology that utilizes adaptive optics (AOSLO) to visualize and target retinal locations on a microscopic level in vivo. Specifically, as a consequence of neuro-degenerative processes, the individual cells of the photoreceptor mosaic may show functional changes (e.g. in their sensitivity to light) before a structural change (e.g. cell loss) is detected. We will develop photoreceptor-resolved functional tests that probe the relationship of retinal structure and function directly and on a cellular scale. These AOSLO-based results may act as sensitive biomarkers of retinal integrity that can be used to better understand disease mechanisms and to track and predict relevant cellular changes during its progression and intervention. If successful, in vivo cellular function testing with AOSLO lessens the need of inefficient, protracted histological validation in the development phase of new treatments, because microscopic physiological changes can be monitored in real-time within the living subject. We will make our results and methods available for other researchers within the SPP as a platform to test newly developed and future therapeutic approaches in treated subjects directly.

目前对患有神经视网膜变性的受试者进行的临床视网膜成像和功能测试不够敏感，无法在时间范围内发现微小但显着的生理变化，而这些变化对于评估新兴的基于基因和细胞的干预工作是可行的。我们的目标是通过最近开发的成像和刺激技术来缩小这一差距，该技术利用自适应光学（AOSLO）在体内微观水平上可视化和靶向视网膜位置。具体地，作为神经退行性过程的结果，在检测到结构变化（例如细胞损失）之前，光感受器镶嵌体的个体细胞可能显示出功能变化（例如它们对光的敏感性）。我们将开发光感受器分辨功能测试，直接在细胞尺度上探测视网膜结构和功能的关系。这些基于AOSLO的结果可以作为视网膜完整性的敏感生物标志物，可用于更好地了解疾病机制，并跟踪和预测其进展和干预期间的相关细胞变化。如果成功的话，AOSLO体内细胞功能测试减少了在新治疗开发阶段进行低效、冗长的组织学验证的需要，因为可以在活体内实时监测微观生理变化。我们将把我们的结果和方法提供给SPP内的其他研究人员，作为一个平台，直接在治疗对象中测试新开发的和未来的治疗方法。