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

机译:具有自适应光学光学相干断层扫描的光感受器椎间盘脱落的跟踪动态

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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:光感受器吸收光引发视觉,但也导致感光体外部区段(OS)中有毒光氧化化合物的积累。为防止这种积累,从OS的远端定期修剪OS光盘的小数据包,该过程称为盘脱落。遗憾的是,脱落事件的任何部分都能导致光感受器和RPE营养不良,并且在许多视网膜疾病中涉及,包括年龄相关的黄斑变性和视网膜炎。虽然对脱落的复杂分子和信号传导途径众所周知,但所有这些进步都在使用后模眼的动物模型中发生。这些转化为生活视网膜和人类的主要障碍。为此,我们最近发现了活性人视网膜中锥形OS圆盘脱落的光学特征,使用配备有自适应光学的光学相干断层扫描,与后处理方法一起追踪和监控4D的单个锥体。在这项研究中,我们在几个关键领域提高了这种方法:将图像采集增加到MHz A扫描速率,提高了检测磁盘脱落事件的可靠性,建立系统精度,以及在整个遮蔽周期上使用锥形跟踪。成千上万的锥体成功成功地成熟并在两个健康的主题中的17小时内进行了成功和跟踪。脱落事件在79.5%和77.4%的履带锥中检测到。与以往的动物研究类似,脱落患病率表现出昼夜节律。但是,我们惊讶地发现,对于这两个主题,在整天中发生脱落,在早晨,频率宽阔,频率降低,频率降低。符合这一点,平均锥形OS长度的痕迹显示在早上和下午和延时的缩减。

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