Department of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, People's Republic of China.
Invest Ophthalmol Vis Sci. 2013 Mar 19;54(3):1988-97. doi: 10.1167/iovs.12-10706.
To elucidate the underlying pathologic mechanism of congenital stationary night blindness (CSNB) by examining the characteristics of electrical signal transmission within the inner retinal circuit after Cacna1f gene mutation.
Retinas isolated from the spontaneous Cacna1f mutant rats or wild-type rats were placed into a recording chamber, with the ganglion cell layer facing the biochip electrode array. The light-driven responses of the retinal ganglion cells (RCGs) were recorded using a multielectrode array (MEA) system. In the electrical stimulus cases, charge-balanced biphasic current pulse trains were generated and applied to the central electrode of MEA to stimulate the RCGs. Chemical compounds were bath-applied through an active perfusion system. The acquired data were further analyzed off-line.
Typical electrical responses were successfully recorded in the retinas of both wild-type rats and Cacna1f gene mutated rats. In the Cacna1f mutant retinas, the amplitude of the light-induced a-wave was decreased, paralleling the vanished b-wave. The responsive a-wave was not blocked by the application of 100 μM 2-amino-4-phosphobutyric acid. The increased spontaneous firing rate and the decreased robustness of light-driven signaling reflected a loss in the ability of ganglion cells to encode visual signals reliably and economically. Moreover, the ON pathway is somehow disconnected from ganglion cells, whereas OFF pathways may be preferentially selected by the CSNB retinas. In the electrical stimulus cases, the long-latency responses of RGCs evoked by the indirect synaptic inputs from outer layers of retina were weaker in the CSNB rats compared with that of SD rats.
Using MEA recording, we provide evidences of functional changes for visual signal pathway plasticity in the Cacna1f mutated retinas. Our results suggest that the dysfunctions in photoreceptor neurotransmitter release and the loss of signaling efficiency both occur during CSNB, and the latter is possibly reversible.
通过研究 Cacna1f 基因突变后内视网膜电路中电信号传递的特征，阐明先天性静止性夜盲症（CSNB）的潜在病理机制。
将自发的 Cacna1f 突变大鼠或野生型大鼠的视网膜置于记录室中，使神经节细胞层朝向生物芯片电极阵列。使用多电极阵列（MEA）系统记录视网膜神经节细胞（RCG）的光驱动反应。在电刺激情况下，生成平衡电荷的双相电流脉冲序列，并将其施加到 MEA 的中央电极以刺激 RCG。通过主动灌注系统对化学化合物进行浴式应用。获取的数据进一步离线分析。
在野生型大鼠和 Cacna1f 基因突变大鼠的视网膜中均成功记录到典型的电反应。在 Cacna1f 突变大鼠的视网膜中，光诱导的 a 波幅度降低，同时 b 波消失。应用 100μM 2-氨基-4-磷酸丁酸不能阻断响应的 a 波。自发放电率增加和光驱动信号的稳健性降低反映了神经节细胞可靠和经济地编码视觉信号的能力丧失。此外，ON 通路与神经节细胞某种程度上断开，而 OFF 通路可能被 CSNB 视网膜优先选择。在电刺激情况下，由外核层间接突触输入引起的 RGC 的长潜伏期反应在 CSNB 大鼠中比在 SD 大鼠中较弱。
使用 MEA 记录，我们提供了 Cacna1f 突变视网膜中视觉信号通路可塑性功能变化的证据。我们的结果表明，在 CSNB 中，光感受器神经递质释放功能障碍和信号效率丧失均发生，后者可能是可逆的。
