Eldred William D, Blute Todd A
Laboratory of Visual Neurobiology, Department of Biology, Boston University, MA 02215, USA.
Vision Res. 2005 Dec;45(28):3469-86. doi: 10.1016/j.visres.2005.07.033. Epub 2005 Sep 19.
Nitric oxide (NO) is the most widespread signaling molecule found in the retina in that it can be made by every retinal cell type. NO is able to influence a wide variety of synaptic mechanisms ranging from increasing or decreasing neurotransmitter release to the modulation of gap junction conductivity. Although biochemical methods can analyze overall levels of NO, such methods cannot indicate the specific cell types involved. In the last few years, fluorescent imaging methods utilizing diaminofluorescein have allowed the real-time visualization of neurochemically or light stimulated NO-induced fluorescence (NO-IF) in specific retinal cells. Recent experiments have shown that this NO-IF can be stabilized using paraformaldehyde fixation. This aldehyde stabilization has allowed the imaging of NO production in the dark and in response to light, as well as the neurochemical modulation of light stimulated NO production. The results of these studies indicate that NO is not always freely diffusible and that NO is largely retained in many cells which make it. The NO production in retina is highly damped in that in the absence of stimulation, the endogenous levels of NO production are extremely low. Finally, different neurochemical or light stimulation protocols activate NO production in specific cells and subcellular compartments. Therefore, although the NO signaling is widespread in retina, it is very selectively activated and has different functions in specific retinal cell types. The use of NO imaging will continue to play a critical role in future studies of the function of NO in retina and other neural systems.
一氧化氮(NO)是视网膜中分布最广泛的信号分子,因为每种视网膜细胞类型都能产生它。NO能够影响多种突触机制,从增加或减少神经递质释放到调节缝隙连接传导性。虽然生化方法可以分析NO的总体水平,但这些方法无法指出涉及的具体细胞类型。在过去几年中,利用二氨基荧光素的荧光成像方法能够实时可视化特定视网膜细胞中神经化学或光刺激诱导的NO荧光(NO-IF)。最近的实验表明,使用多聚甲醛固定可以稳定这种NO-IF。这种醛类固定使得在黑暗中和对光响应时的NO产生成像成为可能,以及对光刺激的NO产生进行神经化学调节。这些研究结果表明,NO并非总是可自由扩散的,而且在许多产生它的细胞中,NO大多是被保留的。视网膜中的NO产生受到高度抑制,因为在没有刺激的情况下,内源性NO产生水平极低。最后,不同的神经化学或光刺激方案会激活特定细胞和亚细胞区室中的NO产生。因此,尽管NO信号在视网膜中广泛存在,但它是非常有选择性地被激活的,并且在特定视网膜细胞类型中具有不同的功能。NO成像的应用将在未来关于NO在视网膜和其他神经系统中功能的研究中继续发挥关键作用。