Pupillary Light Reflexes in Severe Photoreceptor Blindness Isolate the Melanopic Component of Intrinsically Photosensitive Retinal Ganglion Cells.
Pupillary Light Reflexes in Severe Photoreceptor Blindness Isolate the Melanopic Component of Intrinsically Photosensitive Retinal Ganglion Cells.
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DOI：
10.1167/iovs.17-21909
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发表时间：
2017-06-01
影响因子：
4.4
通讯作者：
Cideciyan AV
中科院分区：
文献类型：
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作者：
Charng J;Jacobson SG;Heon E;Roman AJ;McGuigan DB 3rd;Sheplock R;Kosyk MS;Swider M;Cideciyan AV
瞳孔对光反射（PLR）由外部视网膜光感受器和内部视网膜的表达黑视素的固有光敏视网膜神经节细胞驱动。为了分离黑视成分，我们研究了由作用于外层视网膜的基因突变引起的莱伯先天性黑蒙（LCA）导致的严重视力丧失的患者。直接PLR记录在LCA患者（n = 21）与已知的分子原因和严重的视力丧失。在所有患者中使用标准刺激（2.5 log scot-cd.m-2; 2.13 log quanta.cm-2.s-1;消色差全视野），持续时间为0.1秒或5秒。在一个患者子集中，使用更高的亮度（3.9 log scot-cd.m-2）进行额外的记录。LCA患者对短时间的标准刺激没有检测到PLR。在长时间刺激下，大多数患者（18/21）可检测到PLR。PLR的潜伏期为2.8 ± 1.3秒，而正常潜伏期为0.19 ± 0.02秒。患者的峰值收缩幅度在6.2 ± 2.3秒时为1.1 ± 0.9 mm，与3.0 ± 0.4秒时的正常幅度4.2 ± 0.4 mm有显著差异。高亮度的记录表明，在严重的LCA PLRs也可以诱发与短时间的刺激。严重LCA患者的PLR可能代表与视杆细胞和视锥细胞输入隔离的黑视回路的激活。人类黑视PLR的特性的知识不仅允许与动物模型中的那些进行比较，而且还用于定义针对没有外部视网膜功能的患者的临床试验中的视网膜后透射的保真度。
Pupillary light reflex (PLR) is driven by outer retinal photoreceptors and by melanopsin-expressing intrinsically photosensitive retinal ganglion cells of the inner retina. To isolate the melanopic component, we studied patients with severe vision loss due to Leber congenital amaurosis (LCA) caused by gene mutations acting on the outer retina. Direct PLR was recorded in LCA patients (n = 21) with known molecular causation and severe vision loss. Standard stimuli (2.5 log scot-cd.m−2; ∼13 log quanta.cm−2.s−1; achromatic full-field) with 0.1- or 5-second duration were used in all patients. Additional recordings were performed with higher luminance (3.9 log scot-cd.m−2) in a subset of patients. The LCA patients showed no detectable PLR to the standard stimulus with short duration. With longer-duration stimuli, a PLR was detectable in the majority (18/21) of patients. The latency of the PLR was 2.8 ± 1.3 seconds, whereas normal latency was 0.19 ± 0.02 seconds. Peak contraction amplitude in patients was 1.1 ± 0.9 mm at 6.2 ± 2.3 seconds, considerably different from normal amplitude of 4.2 ± 0.4 mm at 3.0 ± 0.4 seconds. Recordings with higher luminance demonstrated that PLRs in severe LCA could also be evoked with short-duration stimuli. The PLR in severe LCA patients likely represents the activation of the melanopic circuit in isolation from rod and cone input. Knowledge of the properties of the human melanopic PLR allows not only comparison to those in animal models but also serves to define the fidelity of postretinal transmission in clinical trials targeting patients with no outer retinal function.