Circadian Rhythms and Sleep Disorders Program, Neuroscience Institute and Department of Pharmacology & Toxicology, Morehouse School of Medicine, 720 Westview Dr. SW, Atlanta, GA 30130, United States.
Neurosci Lett. 2011 Apr 20;494(1):61-4. doi: 10.1016/j.neulet.2011.02.056.
Previous studies have demonstrated that melatonin is effective in lowering intraocular pressure and that it may also protect ganglion cells. We have recently reported that, in mice lacking the melatonin receptors type 1, 25-30% ganglion cells die out by 18months of age, suggesting that these receptors might be important for ganglion cells survival. In this study we show that the loss of ganglion cells is specific for melatonin receptors type 1 knock-out since mice lacking the melatonin receptors type 2 did not show any significant change in the number ganglion cells during aging. Furthermore, we report that melatonin receptors type 1 knock-out mice have higher intraocular pressure during the nocturnal hours than control or melatonin receptors type 2 knock-out mice at 3 and 12months of age. Finally, our data indicate that administration of exogenous melatonin in wild-type, but not in melatonin receptors type 1 knock-out, can significantly reduce intraocular pressure. Our studies indicate that the decreased viability of ganglion cells observed in melatonin receptors type 1 knock-out mice may be a consequence of the increases in the nocturnal intraocular pressure thus suggesting that intraocular pressure levels at night and melatonin signaling should be considered as risk factor in the pathogenesis of glaucoma.
先前的研究表明褪黑素可有效降低眼内压，并且可能对节细胞具有保护作用。我们最近的研究报告显示，在缺乏褪黑素受体 1 型的小鼠中，18 个月大时约有 25-30%的节细胞死亡，这表明这些受体对于节细胞的存活可能很重要。在这项研究中，我们发现节细胞的缺失是特异性的褪黑素受体 1 型敲除，因为缺乏褪黑素受体 2 型的小鼠在衰老过程中节细胞数量没有明显变化。此外，我们报告说，褪黑素受体 1 型敲除小鼠在 3 个月和 12 个月大时的夜间，其眼内压高于对照组或褪黑素受体 2 型敲除小鼠。最后，我们的数据表明，外源性褪黑素在野生型小鼠中给药，但不在褪黑素受体 1 型敲除小鼠中给药，可以显著降低眼内压。我们的研究表明，在褪黑素受体 1 型敲除小鼠中观察到的节细胞活力下降可能是夜间眼内压升高的结果，因此表明夜间眼内压水平和褪黑素信号应被视为青光眼发病机制的危险因素。
