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Tracking dynamics of photoreceptor disc shedding with adaptive optics-optical coherence tomography

机译:自适应光学-光学相干断层扫描技术跟踪感光盘脱落的动力学

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Absorption of light by photoreceptors initiates vision, but also leads to accumulation of toxic photo-oxidative compounds in the photoreceptor outer segment (OS). To prevent this buildup, small packets of OS discs are periodically pruned from the distal end of the OS, a process called disc shedding. Unfortunately dysfunction in any part of the shedding event can lead to photoreceptor and RPE dystrophy, and has been implicated in numerous retinal diseases, including age related macular degeneration and retinitis pigmentosa. While much is known about the complex molecular and signaling pathways that underpin shedding, all of these advancements have occurred in animal models using postmortem eyes. How these translate to the living retina and to humans remain major obstacles. To that end, we have recently discovered the optical signature of cone OS disc shedding in the living human retina, measured noninvasively using optical coherence tomography equipped with adaptive optics in conjunction with post processing methods to track and monitor individual cones in 4D. In this study, we improve on this method in several key areas: increasing image acquisition up to MHz A-scan rates, improving reliability to detect disc shedding events, establishing system precision, and developing cone tracking for use across the entire awake cycle. Thousands of cones were successfully imaged and tracked over the 17 hour period in two healthy subjects. Shedding events were detected in 79.5% and 77.4% of the tracked cones. Similar to previous animal studies, shedding prevalence exhibited a diurnal rhythm. But we were surprised to find that for these two subjects shedding occurred across the entire day with broad, elevated frequency in the morning and decreasing frequency as the day progressed. Consistent with this, traces of the average cone OS length revealed shedding dominated in the morning and afternoon and renewal in the evening.
机译:感光体吸收光会启动视觉,但也会导致有毒的光氧化性化合物在感光体外部(OS)内积聚。为了防止这种堆积,会定期从OS的远端修剪一小包OS光盘,此过程称为光盘脱落。不幸的是,脱落事件的任何部位的功能障碍都可能导致感光细胞和RPE营养不良,并与许多视网膜疾病有关,包括与年龄有关的黄斑变性和色素性视网膜炎。尽管对导致脱落的复杂分子和信号传导途径了解很多,但所有这些进展已经在使用死后眼睛的动物模型中发生。这些如何转化为活的视网膜和人类仍然是主要障碍。为此,我们最近发现了圆锥形OS椎间盘在活的人类视网膜中脱落的光学特征,该特征是使用配备有自适应光学器件的光学相干断层扫描结合后处理方法以4D方式跟踪和监视单个圆锥的无创测量的。在这项研究中,我们在以下几个关键领域对该方法进行了改进:将图像采集提高到MHz A扫描速率,提高了检测光盘脱落事件的可靠性,建立了系统精度,并开发了在整个清醒周期中使用的圆锥跟踪。在两个健康受试者的17小时内,成千上万的视锥细胞已成功成像并跟踪。在跟踪的圆锥体中发现了79.5%和77.4%的脱落事件。与以前的动物研究相似,脱落率表现出昼夜节律。但是我们很惊讶地发现,对于这两个对象,整个一天都发生脱落,早晨的频率广泛,升高,而随着一天的进展频率降低。与此相一致的是,平均圆锥OS长度的痕迹表明,脱落在早晨和下午占主导地位,而在晚上则恢复。

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