Clinical vision and molecular loss: Integrating visual psychophysics with molecular genetics reveals key details of normal and abnormal visual processing.
Clinical vision and molecular loss: Integrating visual psychophysics with molecular genetics reveals key details of normal and abnormal visual processing.
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临床视力和分子损失：将视觉心理物理学与分子遗传学相结合揭示了正常和异常视觉处理的关键细节。
DOI：
10.1016/j.preteyeres.2020.100937
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发表时间：
2021
影响因子：
17.8
通讯作者：
Stockman A
中科院分区：
文献类型：
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作者：
Stockman A
在过去的二十年里，我们开发了技术和模型来研究已知的分子缺陷影响视觉性能的方式。由于视网膜信号中的分子缺陷总是会改变视觉处理的速度，我们的策略一直是测量由此产生的闪烁敏感度的变化。闪烁测量不仅提供了对视觉表现的直接临床评估，而且还揭示了关于异常和正常视觉系统功能的基本细节。在这里，我们汇集了我们过去对GNA2、RGS9、GUCA1A、RPE65、OPA1、KCNV2和NR2E3基因变异患者的测量结果，并使用标准的视觉处理模型分析结果。该模型将闪烁敏感性视为一系列简单处理步骤的结果，其中一个或多个步骤会因基因缺陷而改变。我们的分析表明，大多数缺陷直接减慢了视觉反应，但也有一些加速了视觉反应。然而，至关重要的是，处理序列中的其他步骤可以进行补偿性调整，以抵消异常。例如，如果异常步骤减慢了视觉响应，则另一个步骤可能会加速或减弱响应，以重新平衡系统性能。这种补偿性调整很可能是按顺序进行的，通常会适应不断变化的光照水平。我们的技术和建模也使我们能够梳理出静止和渐进的影响，局部的分子损失帮助我们解开正常和异常处理序列中的个别步骤并确定其特征。
Over the past two decades we have developed techniques and models to investigate the ways in which known molecular defects affect visual performance. Because molecular defects in retinal signalling invariably alter the speed of visual processing, our strategy has been to measure the resulting changes in flicker sensitivity. Flicker measurements provide not only straightforward clinical assessments of visual performance but also reveal fundamental details about the functioning of both abnormal and normal visual systems. Here, we bring together our past measurements of patients with pathogenic variants in theGNAT2,RGS9,GUCA1A,RPE65,OPA1, KCNV2andNR2E3genes and analyse the results using a standard model of visual processing. The model treats flicker sensitivity as the result of the actions of a sequence of simple processing steps, one or more of which is altered by the genetic defect. Our analyses show that most defects slow down the visual response directly, but some speed it up. Crucially, however, other steps in the processing sequence can make compensatory adjustments to offset the abnormality. For example, if the abnormal step slows down the visual response, another step is likely to speed up or attenuate the response to rebalance system performance. Such compensatory adjustments are probably made by steps in the sequence that usually adapt to changing light levels. Our techniques and modelling also allow us to tease apart stationary and progressive effects, and the localised molecular losses help us to unravel and characterise individual steps in the normal and abnormal processing sequences.