Multimodal assessment of photoreceptor structure and function in retinal trauma

项目摘要 视杆和视锥光感受器通过光转导将光转换成电信号来启动视觉。 许多条件直接或间接地禁止感光器功能，包括遗传性视网膜条件， 全身性疾病、神经系统疾病和创伤性损伤。临床目标是识别病理， 防止未来的损害，并理想地恢复失去的功能。视觉研究已经投入了巨大的努力， 恢复视力治疗，但技术需要准确地检测视网膜的变化和监测视网膜 在临床环境中恢复仍然有限。视网膜外伤引起的视觉障碍是视力下降的常见原因 损失往往随着时间的推移解决-提供了一个很好的模型，以表征和改善临床技术 用于检测视网膜异常和监测视网膜恢复。普遍的临床测试，以评估视网膜 结构和功能，包括光学相干断层扫描（OCT）、微视野检查和最佳矫正视力 视力（BCVA）是低分辨率和/或主观的。因此，迫切需要改善生物标志物， 视网膜病理学的检测和新方法的应用，以更好地了解 创伤性视力丧失和视网膜恢复的病理生理学。在这个项目中，自适应光学扫描光 检眼镜检查（AOSLO）-一种能够进行高分辨率体内成像和功能评估的技术， 光感受器-将用于评估基于AO的光感受器指标与 临床使用的工具。我们的中心假设是，多模式评估感光器结构和 功能将揭示感光器指标的变化，这些指标可以转化为状态的生物标志物， 健康和患病视网膜的功能。第一个具体的目标是确定细胞相关的锥 光感受器生物标志物的临床工具。具体而言，我们将使用AOSLO检查常规临床 工具，OCT和微视野检查。第二个具体目标是评估在视网膜中的视锥光感受器结构。 轻度创伤性脑损伤（TBI）患者。视觉功能障碍通常在轻度TBI后报告， 无临床眼科发现。我们假设临床诊断为轻度TBI的个体， 随后视觉功能障碍将具有亚临床感光器结构和功能异常。的 第三个具体目的是鉴定黄斑裂孔修复后视锥光感受器恢复的机制。 黄斑裂孔修复后视力恢复的理论存在竞争，涉及感光细胞 光感受器外节结构随时间的迁移或恢复。本研究计划提供 通过结合体内视网膜成像，视网膜和视网膜之间的转换， 神经系统疾病、光学设计、软件开发和生物医学工程。这一提议创造了 一个理想的平台，以发展一个独立的翻译科学家所需的补充技能，如 扩大我的技术敏锐度，改善科学交流，发展指导技能， 拓展我的专业网络

PROJECT SUMMARY Rod and cone photoreceptors initiate vision by converting light into an electrical signal via phototransduction. Many conditions either directly or indirectly prohibit photoreceptor function, including inherited retinal conditions, systemic diseases, neurological disorders, and traumatic injuries. Clinical objectives are to identify pathology, prevent future damage, and ideally restore lost function. Vision research has placed tremendous efforts on restorative vision treatments, but the technology required to accurately detect retinal changes and monitor retinal recovery remains limited in clinical settings. Visual deficits induced by retinal trauma is a common cause of vision loss that often resolves over time – providing an excellent model to characterize and improve clinical techniques for detecting retinal abnormalities and monitoring retinal restoration. Ubiquitous clinical tests to assess retinal structure and function, including optical coherence tomography (OCT), microperimetry, and best-corrected visual acuity (BCVA), are low resolution and/or subjective. There is thus a critical need to improve biomarkers for detection of retinal pathology and application of novel approaches for better understanding behind the pathophysiology of traumatic vision loss and retinal recovery. In this project, adaptive optics scanning light ophthalmoscopy (AOSLO) – a technique enabling high-resolution in vivo imaging and functional assessment of photoreceptors – will be utilized to assess the relationship between AO-based photoreceptor metrics and clinically used tools. Our central hypothesis is that multi-modal assessment of photoreceptor structure and function will reveal variations in photoreceptor metrics that can be translated into biomarkers for the status and function of the healthy and diseased retina. The first specific aim is to identify cellular correlates of cone photoreceptor biomarkers from clinical tools. Specifically, we will use AOSLO to examine conventional clinical tools, OCT and microperimetry. The second specific aim is to assess cone photoreceptor structure in individuals with mild traumatic brain injury (TBI). Visual dysfunction is commonly reported following mild TBI with no clinical ophthalmic findings. We hypothesize that individuals with a clinical diagnosis of mild TBI and subsequent visual dysfunction will have subclinical photoreceptor structural and functional abnormalities. The third specific aim is to identify the mechanism of cone photoreceptor recovery following macular hole repair. There are competing theories of visual recovery following macular hole repair, implicating either photoreceptor migration or recovery of photoreceptor outer segment structure over time. The research planned herein provides a unique individualized training opportunity by combining in vivo retinal imaging, translation between retinal and neurological disorders, optical design, software development, and biomedical engineering. This proposal creates an ideal platform to develop complementary skills required for an independent translational scientist, such as broadening my technical acumen, improving scientific communication, developing mentoring skills, and expanding my professional network.