Li Yichao, Cohen Ethan D, Qian Haohua
Visual Function Core, National Eye Institute (NEI), National Institutes of Health, Bethesda, MD, United States.
Division of Biomedical Physics, Office of Science and Engineering Labs, Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, MD, United States.
Front Cell Neurosci. 2020 Sep 25;14:566712. doi: 10.3389/fncel.2020.566712. eCollection 2020.
Light adaptation changes both the sensitivity and maximum amplitude (R) of the mouse photopic electroretinogram (ERG) b-wave. Using the ERG, we examined how modulation of gap junctional coupling between rod and cones alters the light-adapted ERG. To measure changes, a b-wave light adaptation enhancement factor (LAEF), was defined as the ratio of R after 15 min light adaptation to R recorded at the onset of an adapting light. For wild-type mice (WT), the LAEF averaged 2.64 ± 0.29, however, it was significantly reduced (1.06 ± 0.04) for connexin 36 knock out (Cx36KO) mice, which lack electrical coupling between photoreceptors. Wild type mice intraocularly injected with meclofenamic acid (MFA), a gap junction blocker, also showed a significantly reduced LAEF. Degeneration of rod photoreceptors significantly alters the effects of light adaptation on the photopic ERG response. Rd10 mice at P21, with large portions of their rod photoreceptors present in the retina, exhibited a similar b-wave enhancement as wildtype controls, with a LAEF of 2.55 ± 0.19. However, by P31 with most of their rod photoreceptors degenerated, rd10 mice had a much reduced b-wave enhancement during light-adaptation (LAEF of 1.54 ± 0.12). Flicker ERG responses showed a higher temporal amplitude in mesopic conditions for WT than those of Cx36KO mice, suggesting rod-cone coupling help high-frequency signals to pass from rods to cone pathways in the retina. In conclusion, our study provides a novel method to noninvasively measure the dynamics and modulation by the light adaptation for rod-cone gap junctional coupling in intact eyes.
明适应会改变小鼠明视视网膜电图（ERG）b波的敏感度和最大振幅（R）。我们利用ERG研究了视杆细胞和视锥细胞之间缝隙连接耦合的调制如何改变明适应ERG。为了测量变化，定义了一个b波明适应增强因子（LAEF），即15分钟明适应后的R与适应光开始时记录的R的比值。对于野生型小鼠（WT），LAEF平均为2.64±0.29，然而，对于缺乏光感受器之间电耦合的连接蛋白36基因敲除（Cx36KO）小鼠，LAEF显著降低（1.06±0.04）。眼内注射缝隙连接阻滞剂甲氯芬那酸（MFA）的野生型小鼠也表现出LAEF显著降低。视杆光感受器的退化显著改变了明适应对明视ERG反应的影响。P21时视网膜中存在大部分视杆光感受器的Rd10小鼠表现出与野生型对照相似的b波增强，LAEF为2.55±0.19。然而，到P31时，大多数视杆光感受器退化，Rd10小鼠在明适应期间b波增强明显降低（LAEF为1.54±0.12）。闪烁ERG反应显示，在中间视觉条件下，WT小鼠的时间振幅高于Cx36KO小鼠，这表明视杆-视锥耦合有助于高频信号从视杆细胞传递到视网膜中的视锥细胞通路。总之，我们的研究提供了一种新方法，用于在完整眼睛中无创测量视杆-视锥缝隙连接耦合的光适应动力学和调制。
