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

目前临床视网膜成像和功能测试对患有神经视网膜变性的受试者不够敏感，无法在时间框架内发现微小但重要的生理变化，这些变化对于评估新兴的基因和基于细胞的干预措施是可行的。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定位视网膜位置。具体来说，作为神经退行性过程的结果，光感受器马赛克的单个细胞可能在检测到结构变化（例如细胞损失）之前显示功能变化（例如对光的敏感性）。我们将开发光感受器解析功能测试，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aoso的结果可能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，并在其进展和干预过程中跟踪和预测相关的细胞变化。如果成功，利用AOSLO进行的体内细胞功能测试减少了在新疗法开发阶段低效、冗长的组织学验证的需要，因为微观生理变化可以在活体中实时监测。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。

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.