Visual consequences of molecular changes in the guanylate cyclase-activating protein.
Visual consequences of molecular changes in the guanylate cyclase-activating protein.
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DOI：
10.1167/iovs.13-13682
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发表时间：
2014-03
影响因子：
4.4
通讯作者：
A. Stockman;G. Henning;A. T. Moore;A. T. Moore;A. R. Webster;A. R. Webster;Michel Michaelides;Michel Michaelides;C. Ripamonti
中科院分区：
文献类型：
--
作者：
A. Stockman;G. Henning;A. T. Moore;A. T. Moore;A. R. Webster;A. R. Webster;Michel Michaelides;Michel Michaelides;C. Ripamonti
我们对4名年龄在39 - 55岁之间的家族成员的鸟苷酸环化酶激活蛋白-1（GCAP 1）Tyr 99 Cys突变相关的视觉表现变化进行了表征和建模。鸟苷酸环化酶及其激活蛋白是视觉信号转导途径中的分子，在其光激活水解后恢复环GMP（cGMP）。这种突变导致在黑暗中cGMP过量，导致进行性光感受器丧失。方法测量L-视锥的时间视敏度作为目标辐照度的函数，测量L-视锥的时间对比敏感度作为时间频率的函数。结果所有四个突变GCAP 1家族成员表现出相对于正常观察者的灵敏度或敏锐度损失。最年轻的家庭成员的数据与相对于正常人的视觉反应的异常加速一致，但老年成员的数据显示出与其反应减慢一致的频率灵敏度逐渐升高。结论：最年轻的观察者视觉反应的加速与Tyr 99 Cys突变一致，该突变导致光照后cGMP的更快替换，因此，与正常人相比，时间积分减少，高频灵敏度相对改善。老年观察者的高频损失与他们的视野受到某些缓慢过程的限制是一致的。这可能是由于一些残留或故障的分子过程限制受损的光感受器内的转导或从一个主动或被动的postreceptoral重组功能的光感受器的缺乏所造成的。
PURPOSE We characterized and modeled changes in visual performance associated with a Tyr99Cys mutation in guanylate cyclase-activating protein-1 (GCAP1) in four family members aged between 39 and 55 years old. Guanylate cyclase and its activating protein are molecules in the visual transduction pathway that restore cyclic GMP (cGMP) following its light-activated hydrolysis. The mutation causes an excess of cGMP in the dark and results in progressive photoreceptor loss. METHODS L-cone temporal acuity was measured as a function of target irradiance, and L-cone temporal contrast sensitivity was measured as a function of temporal frequency. RESULTS All four mutant GCAP1 family members showed sensitivity or acuity losses relative to normal observers. The data for the youngest family member are consistent with an abnormal speeding up of the visual response relative to that in normals, but those for the older members showed a progressively higher-frequency sensitivity loss consistent with a slowing down of their response. CONCLUSIONS The speeding up of the visual response in the youngest observer is consistent with the Tyr99Cys mutation that results in the more rapid replacement of cGMP after light exposure and, thus, in a reduction of temporal integration and relative improvement in high-frequency sensitivity compared to normals. The high-frequency losses in the older observers are consistent with their vision being limited by the interposition of some sluggish process. This might result from some residual or malfunctioning molecular process limiting transduction within damaged photoreceptors or from an active or passive postreceptoral reorganization caused by the paucity of functioning photoreceptors.