PDF(Pubmed)
Abstract：
Transient receptor potential canonical (TRPC) channels are calcium channels with diverse expression profiles and physiological implications in the retina. Neurons and glial cells of rat retinas with photoreceptor degeneration caused by retinitis pigmentosa (RP) exhibit basal calcium levels that are above those detected in healthy retinas. Inner retinal cells are the last to degenerate and are responsible for maintaining the activity of the visual cortex, even after complete loss of photoreceptors. We considered the possibility that TRPC1 and TRPC5 channels might be associated with both the high calcium levels and the delay in inner retinal degeneration. TRPC1 is known to mediate protective effects in neurodegenerative processes while TRPC5 promotes cell death. In order to comprehend the implications of these channels in RP, the co-localization and subsequent physical interaction between TRPC1 and TRPC5 in healthy retina (Sprague-Dawley rats) and degenerating (P23H-1, a model of RP) retina were detected by immunofluorescence and proximity ligation assays. There was an overlapping signal in the innermost retina of all animals where TRPC1 and TRPC5 physically interacted. This interaction increased significantly as photoreceptor loss progressed. Both channels function as TRPC1/5 heteromers in the healthy and damaged retina, with a marked function of TRPC1 in response to retinal degenerative mechanisms. Furthermore, our findings support that TRPC5 channels also function in partnership with STIM1 in Müller and retinal ganglion cells. These results suggest that an increase in TRPC1/5 heteromers may contribute to the slowing of the degeneration of the inner retina during the outer retinal degeneration.
摘要：
瞬时受体电位规范（TRPC）通道是钙通道，在视网膜中具有不同的表达谱和生理意义。由色素性视网膜炎（RP）引起的光感受器变性的大鼠视网膜的神经元和神经胶质细胞表现出高于健康视网膜中检测到的基础钙水平。内部视网膜细胞是最后退化的细胞，负责维持视觉皮层的活动，即使在光感受器完全丧失之后。我们认为TRPC1和TRPC5通道可能与高钙水平和内部视网膜变性的延迟有关。已知TRPC1在神经变性过程中介导保护作用,而TRPC5促进细胞死亡。为了理解这些渠道在RP中的含义，通过免疫荧光和邻近连接试验检测了TRPC1和TRPC5在健康视网膜(Sprague-Dawley大鼠)和退化视网膜(P23H-1,一种RP模型)中的共定位和随后的物理相互作用.在TRPC1和TRPC5物理相互作用的所有动物的最内层视网膜中存在重叠信号。这种相互作用随着光感受器损失的进展而显著增加。在健康和受损的视网膜中，两个通道都充当TRPC1/5异聚体，具有明显的TRPC1功能，以响应视网膜变性机制。此外，我们的研究结果支持TRPC5通道在Müller和视网膜神经节细胞中也与STIM1协同发挥作用.这些结果表明，TRPC1/5异聚体的增加可能有助于在外部视网膜变性过程中减缓内部视网膜的变性。
