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 the GNAT2, RGS9, GUCA1A, RPE65, OPA1, KCNV2 and NR2E3 genes 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.

在过去的二十年里，我们开发了技术和模型来研究已知分子缺陷影响视觉性能的方式。因为视网膜信号中的分子缺陷总是会改变视觉处理的速度，所以我们的策略是测量由此产生的闪烁敏感性变化。闪烁测量不仅提供了对视觉性能的直接临床评估，而且还揭示了异常和正常视觉系统功能的基本细节。在这里，我们汇总了我们过去对GNAT2、RGS9、GUCA1A、RPE65、OPA1 、 KCNV2和NR2E3致病变异患者的测量结果基因并使用视觉处理的标准模型分析结果。该模型将闪烁敏感性视为一系列简单处理步骤操作的结果，其中一个或多个被遗传缺陷改变。我们的分析表明，大多数缺陷会直接减慢视觉响应，但有些会加速。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，另一个步骤可能会加快或减弱响应以重新平衡系统性能。这种补偿性调整可能是通过通常适应不断变化的光照水平的顺序中的步骤进行的。我们的技术和建模也让我们能够区分静止和渐进的效果，