生物谷报道:最近,布朗大学的一个研究组的研究人员发现一种叫做黑视素(melanopsin)的蛋白对眼睛中的一种叫做ipRGCs(注:intrinsically photosensitive retinal ganglion cells)的细胞的内部工作很重要。这项研究公布在近期的《自然》杂志上。研究首次给出证据证明黑视素是一种功能性感光色素。
研究人员发现黑视素能吸收光并引发一种使细胞给大脑发出光信息的生化级联反应。通过这些信号,ipRGCs能够根据日出日落校准身体律节。这种生理节律控制着警戒、睡眠、激素产生、体温和器官功能。这个研究组在2002年发现了ipRGCs,他们的研究表明杆状细胞和锥状细胞并不是仅有的感光眼细胞。
这项研究表明黑视素能吸收光并开启细胞中的一个化学反应链,从而引起电势反应。研究还表明黑视素在结节细胞光受体中扮演一定的角色——它能帮助细胞给大脑发送一种强烈的信号并让大脑知道是白天还是黑夜。
实验中,研究组将黑视素插入到培养的肾细胞中。正常情况下,这些细胞没有感光功能。但是当加入了黑视素时,这些细胞竟变成了光受体。事实上,这些肾脏细胞对光的反应方式基本上与ipRGCs相同。这一点也证实了黑视素是结节细胞光受体的感光色素。
研究人员还发现由黑视素开启的生化级联与无脊椎动物如果蝇的眼睛细胞中的反应很相似。这些结果可能告诉我们在进化中,这是一种极其古老的系统,而且我们的眼睛可能还保留着一点无脊椎动物的特征。
由神经学科学家David Berson领导的布朗大学研究组近日发现一种对眼睛中类似蜘蛛细胞的内部功能起着重要作用的黑视素蛋白,也被称为内在感光视网膜中心细胞(ipRGCs)。黑视素吸收光线并引发产生一个生化通道,允许细胞发送光线的信号。通过这些信号,ipRGCs同身体的日常节奏,日升日落保持一致,以24小时为周期控制人体的警觉,睡眠,激素量,体温和器官功能。
布朗大学研究组并惊人地发现了杆细胞和锥形细胞不是唯一的感光眼细胞。像杆细胞和锥形细胞一样,ipRGCs将光能转换成电子信号。但是杆细胞和锥形细胞靠探测物体,颜色和移动来帮助视觉,而ipRGCs却能够测量全部光强,仅仅计算数百万的眼细胞中1,000至2,000个 ipRGCs,会发现它们是截然不同的。它们与大脑有直接的联系,将信息输送至一个控制与光和黑暗环境有关的生物钟很小的区域,同时也调控眼睛瞳孔的收缩。Berson说,这是眼睛中通用的一个光检测系统。他的研究目的就在于提供这个系统如何运作更多的细节信息。
已发表在近期的自然杂志上的这项研究结果,验证了黑视素是具有功能性的视觉感光色素,这种蛋白能吸收光,引起细胞中一系列的化学反应,从而引发一个电子回应。研究也表明,黑视素对中心细胞的光接受器有作用,有助于它们发送一个强信号到大脑以指示白天或者黑夜。
研究小组将黑视素插入从肾脏中提取和体外培养的细胞中发现了这个结果。这些正常情况下对光不敏感的细胞,在黑视素浸泡中,被转入光感受器。实际上,这些肾脏细胞对光的反应几乎与ipRGCs一致,证明了黑视素是中心细胞光感受器的感光色素。
Berson说,这解决了一个关于这些细胞功能的重要问题。Berson和他的研究小组也有另外一个非常有趣的发现,由黑视素激发的生化通道,相对于如老鼠,猴子和人等脊椎动物而言,更靠近那些果蝇和鱿鱼等无脊椎动物的眼细胞。这个结果也可能表示这是一个极其古老的无脊椎动物系统(http://www.bioon.com/)。
Brown Scientists Uncover Inner Workings of Rare Eye Cells
Melanopsin, they found, absorbs light and triggers a biochemical cascade that allows the cells to signal the brain about brightness. Through these signals, ipRGCs synchronize the body's daily rhythms to the rising and setting of the sun. This circadian rhythm controls alertness, sleep, hormone production, body temperature and organ function.
Brown researchers, led by neuroscientist David Berson, announced the discovery of ipRGCs in 2002. Their work was astonishing: Rods and cones aren't the only light-sensitive eye cells.
Like rods and cones, ipRGCs turn light energy into electrical signals. But while rods and cones aid sight by detecting objects, colors and movement, ipRGCs gauge overall light intensity. Numbering only about 1,000 to 2,000 out of millions of eyes cells, ipRGCs are different in another way: They have a direct link to brain, sending a message to the tiny region that controls the body clock about how light or dark the environment is. The cells are also responsible for narrowing the pupil of the eye.
"It's a general brightness detection system in the eye," said Berson, the Sidney A. Fox and Dorothea Doctors Fox Professor of Ophthalmology and Visual Sciences. "What we've done now is provide more details about how this system works."
The research, published in the current issue of Nature, provides the first evidence that melanopsin is a functional sensory photopigment. In other words, this protein absorbs light and sets off a chain of chemical reactions in a cell that triggers an electrical response. The study also showed that melanopsin plays this role in ganglion-cell photoreceptors, helping them send a powerful signal to the brain that it is day or night.
The team made the discovery by inserting melanopsin into cells taken from the kidneys and grown in culture. These cells, which are not normally sensitive to light, were transformed into photoreceptors when flooded with melanopsin. In fact, the kidney cells responded to light almost exactly the way ipRGCs do, confirming that melanopsin is the photopigment for ganglion-cell photoreceptors.
"This resolves a key question about the function of these cells," Berson said. "And so little is known about them, anything we learn is important."
Berson and his team made another intriguing finding: The biochemical cascade sparked by melanopsin is closer to that of eye cells in invertebrates like fruit flies and squid than in spined animals such as mice, monkeys or humans.
"The results may well tell us that this is an extremely ancient system in terms of evolution," Berson said. "We may have a bit of the invertebrate in our eyes."
The research team from Brown included lead author and post-doctoral research associate Xudong Qiu and post-doctoral research associate Kwoon Wong, both in the Department of Neuroscience, as well as graduate students Stephanie Carlson and Vanitha Krishna in the Neuroscience Graduate Program. Tida Kumbalasiri and Ignacio Provencio from the Uniformed Services University of the Health Sciences also contributed to the research.
The National Institutes of Health funded the work.
Source: Brown University