The TRPC5 ion channel is activated upon depletion of intracellular calcium stores, as well as by various stimuli such as nitric oxide (NO), membrane stretch, and cold temperatures. TRPC5 is abundantly expressed in the central nervous system where it has important neuronal functions. In the chick retina, TRPC5 expression was shown to be restricted to amacrine cells (ACs) and Müller glial cells, although its expression was also observed in the ganglion cell layer (GCL) in displaced ACs, as determined by their characteristic cell morphology. However, it is possible that this expression analysis alone might be insufficient to fully understand the expression of TRPC5 in retinal ganglion cells (RGCs). Hence, we analyzed TRPC5 expression by in situ hybridization and immunostaining in the developing mouse retina, and for the first time identified that developing and mature RGCs strongly express TRPC5. The expression begins at E14.5, and is restricted to ACs and RGCs. It was reported that TRPC5 negatively regulates axonal outgrowth in hippocampal neurons. We thus hypothesized that TRPC5 might have similar functions in RGCs since they extend very long axons toward the brain, and this characteristic significantly differs from other retinal cell types. To elucidate its possible involvement in axonal outgrowth, we inhibited TRPC5 activity in developing RGCs which significantly increased RGC axon length. In contrast, overexpression of TRPC5 inhibited axonal outgrowth in developing RGCs. These results indicate that TRPC5 is an important negative regulator of RGC axonal outgrowth. Since TRPC5 is a mechanosensor, it might function to sense abnormal intraocular pressure changes, and could contribute to the death of RGCs in diseases such as glaucoma. In this case, excessive Ca2+ entry through TRPC5 might induce dendritic and axonal remodeling, which could lead to cell death, as our findings clearly indicate that TRPC5 is an important regulator of neurite remodeling.

中文翻译：

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TRPC5 调节发育中的视网膜神经节细胞的轴突生长。

TRPC5 离子通道在细胞内钙储存耗尽以及各种刺激（例如一氧化氮 (NO)、膜拉伸和低温）时被激活。TRPC5 在中枢神经系统中大量表达，它具有重要的神经元功能。在鸡视网膜中，TRPC5 的表达被证明仅限于无长突细胞 (ACs) 和 Müller 神经胶质细胞，尽管它的表达也在移位的 ACs 的神经节细胞层 (GCL) 中观察到，这是由它们的特征细胞形态决定的。然而，仅此表达分析可能不足以完全理解 TRPC5 在视网膜神经节细胞 (RGC) 中的表达。因此，我们在发育中的小鼠视网膜中通过原位杂交和免疫染色分析了 TRPC5 表达，并首次发现发育中和成熟的 RGC 强烈表达 TRPC5。该表达式从 E14.5 开始，仅限于 AC 和 RGC。据报道，TRPC5 负向调节海马神经元的轴突生长。因此我们假设 TRPC5 可能在 RGC 中具有相似的功能，因为它们向大脑延伸很长的轴突，并且这一特征与其他视网膜细胞类型明显不同。为了阐明它可能参与轴突生长，我们在显着增加 RGC 轴突长度的发育 RGC 中抑制了 TRPC5 活性。相反，TRPC5 的过表达抑制了发育中的 RGC 的轴突生长。这些结果表明 TRPC5 是 RGC 轴突生长的重要负调节因子。由于 TRPC5 是一个机械传感器，它可能起到感知异常眼压变化的作用，并可能导致 RGC 在青光眼等疾病中死亡。在这种情况下，过多的 Ca2+ 通过 TRPC5 进入可能会诱导树突和轴突重塑，这可能导致细胞死亡，因为我们的研究结果清楚地表明 TRPC5 是神经突重塑的重要调节因子。