Wood John P M, Chidlow Glyn, Graham Mark, Osborne Neville N
Nuffield Laboratory of Ophthalmology, University of Oxford, Oxford, UK.
J Neurochem. 2005 May;93(3):686-97. doi: 10.1111/j.1471-4159.2005.03059.x.
The process of metabolic coupling has been described as a means of providing additional fuel for neurons during periods of intense activity. This process has been suggested to occur in the mammalian retina, but whether retinal neurons can metabolise glial-derived monocarboxylates remains uncertain. The present study therefore sought to define the preferred energy substrates for maintenance of different retinal cells in culture, in order to clarify whether metabolic coupling can potentially occur in this tissue. All cells in rat retinal cultures were detrimentally affected by glucose deprivation. The effect on some neurons, however, could be partially reversed by 5 mm pyruvate or lactate. Furthermore, the glycolytic inhibitor, iodoacetic acid, caused a dose-dependent loss of all retinal cells in culture, whereas the mitochondrial inhibitor, 2,4-dinitrophenol, only led to a decrease in the number of neurons. Finally, inhibition of transporters for glucose or monocarboxylates caused the respective loss of glia or neurons from cultures. These data together demonstrate that, although cells do preferentially metabolise glucose, monocarboxylates such as lactate or pyruvate do play an important role in neuronal maintenance. These data therefore give partial support to the notion that metabolic coupling may occur in the retina.
代谢偶联过程被描述为在神经元剧烈活动期间为其提供额外燃料的一种方式。有人认为这一过程发生在哺乳动物视网膜中，但视网膜神经元是否能够代谢神经胶质细胞衍生的单羧酸仍不确定。因此，本研究试图确定培养中维持不同视网膜细胞的首选能量底物，以阐明该组织中是否可能发生代谢偶联。大鼠视网膜培养物中的所有细胞都受到葡萄糖剥夺的不利影响。然而，5 mM丙酮酸或乳酸可部分逆转对某些神经元的影响。此外，糖酵解抑制剂碘乙酸导致培养物中所有视网膜细胞呈剂量依赖性损失，而线粒体抑制剂2,4-二硝基苯酚仅导致神经元数量减少。最后，抑制葡萄糖或单羧酸转运体分别导致培养物中神经胶质细胞或神经元的损失。这些数据共同表明，尽管细胞确实优先代谢葡萄糖，但乳酸或丙酮酸等单羧酸在神经元维持中确实发挥着重要作用。因此，这些数据部分支持了视网膜中可能发生代谢偶联的观点。
