Southwest Hospital, Southwest Eye Hospital, Third Military Medical University, Chongqing, 400038, China.
J Mol Neurosci. 2013 Nov;51(3):976-85. doi: 10.1007/s12031-013-0082-9. Epub 2013 Aug 10.
All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.
所有人都知道，色素性视网膜炎（RP）是一组遗传性视网膜退行性疾病，其特征是感光器的进行性功能障碍，并伴有进行性细胞丧失；然而，对于感光器和视锥细胞的丧失如何影响存活的视网膜内层神经元和网络，人们知之甚少。视网膜神经节细胞（RGCs）从视网膜处理和传输视觉信息到大脑中的视觉中枢。健康的各种离子通道决定了 RGCs 对视觉信号的正常接收和投射。先前关于皇家外科医生学院（RCS）大鼠的研究，作为一种经典的 RP 动物模型，表明在 RCS 大鼠视网膜退化的晚期，RGCs 也受到形态和功能的影响。在这里，用 Fluorogold 对 RGCs 进行逆行标记，以研究视网膜退化过程中 RGCs 的分布、密度和形态变化。然后，进行膜片钳记录、western blot 和免疫荧光染色，以研究 RGCs 的钠和钾通道特性，从而探索理解 RGCs 膜特性和放电功能改变的分子和蛋白质基础。我们发现，在视网膜退化的晚期，RGCs 的静息膜电位、输入电阻和电容发生了显著变化。部分 RGCs 不能引发动作电位。内向钠电流和外向钾电流记录表明，钠电流严重受损，但钾电流仅轻微受损。在视网膜退化的晚期，钠通道蛋白的表达明显受损。结果表明，RGCs 的密度降低，突起分支受损，钠离子通道蛋白破坏，导致 RGCs 的电生理功能受损，最终导致视觉功能丧失。
