Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor
Melatonin modulates visual function and cell viability in the mouse retina via the MT1 melatonin receptor
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DOI：
10.1073/pnas.0904400106
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发表时间：
2009-09-01
影响因子：
11.1
通讯作者：
Tosini, Gianluca
中科院分区：
文献类型：
--
作者：
Baba, Kenkichi;Pozdeyev, Nikita;Tosini, Gianluca
褪黑素及其受体在特定视网膜功能中的作用缺乏明确的证据。本研究观察了MT1受体在野生型(WT)和MT1受体缺陷小鼠视网膜内的分布、暗视和明视视网膜电信号(ERG)及视网膜形态。MT1受体转录本定位于光感受器细胞和部分视网膜内神经元。WT小鼠的暗适应ERG反应有昼夜节律，夜间a波和b波幅度较高，但缺乏MT1受体的小鼠则没有这种节律。白天注射褪黑激素降低了WT小鼠的暗视反应阈值和a波和b波的幅度，但对MT1(-/-)小鼠没有影响。研究了MT1受体缺陷对3个不同月龄(3、12和18个月)视网膜形态的影响。MT1(-/-)和WT小鼠在3月龄时没有差异，而在12个月时，MT1(-/-)小鼠外核层的光感受器核数量与WT对照组相比显著减少。12月龄时内核层细胞数和神经节细胞数无明显差异。18月龄时，外核层感光核团的丢失进一步加重，神经节细胞数也明显低于对照组。这些数据证明了褪黑素和MT1受体在哺乳动物视网膜中的功能意义，并为未来褪黑素治疗视网膜变性的研究奠定了基础。
A clear demonstration of the role of melatonin and its receptors in specific retinal functions is lacking. The present study investigated the distribution of MT1 receptors within the retina, and the scotopic and photopic electroretinograms (ERG) and retinal morphology in wildtype (WT) and MT1 receptor-deficient mice. MT1 receptor transcripts were localized in photoreceptor cells and in some inner retinal neurons. A diurnal rhythm in the dark-adapted ERG responses was observed in WT mice, with higher a- and b-wave amplitudes at night, but this rhythm was absent in mice lacking MT1 receptors. Injection of melatonin during the day decreased the scotopic response threshold and the amplitude of the a- and b-waves in the WT mice, but not in the MT1(-/-) mice. The effects of MT1 receptor deficiency on retinal morphology was investigated at three different ages (3, 12, and 18 months). No differences between MT1(-/-) and WT mice were observed at 3 months of age, whereas at 12 months MT1(-/-) mice have a significant reduction in the number of photoreceptor nuclei in the outer nuclear layer compared with WT controls. No differences were observed in the number of cells in inner nuclear layer or in ganglion cells at 12 months of age. At 18 months, the loss of photoreceptor nuclei in the outer nuclear layer was further accentuated and the number of ganglion cells was also significantly lower than that of controls. These data demonstrate the functional significance of melatonin and MT1 receptors in the mammalian retina and create the basis for future studies on the therapeutic use of melatonin in retinal degeneration.