Blind humans lacking rods and cones retain normal responses to nonvisual effects of light

December 13, 2007

In addition to allowing us to see, the mammalian eye also detects light for a number of "non-visual" phenomena. A prime example of this is the timing of the sleep/wake cycle, which is synchronized by the effects of light on the circadian pacemaker in the hypothalamus.

In a study published online on December 13th in Current Biology, researchers have identified two totally blind humans whose non-visual responses to light remain intact, suggesting that visual and non-visual responses to light are functionally distinct. Indeed, this separation was suggested by earlier studies in mice that demonstrated that circadian rhythms and other non-visual responses remain sensitive to light in the absence of rods and cones, the two photoreceptor types that are responsible for vision.

It turns out that mammals have an additional light-sensitive photoreceptor in the retinal ganglion cell layer (pRGCs) that is directly sensitive to light and is primarily responsible for mediating these responses. These cells are most sensitive to short-wavelength light with a peak sensitivity at ~480 nm, in the visible blue light range. While these studies and others in sighted subjects suggested that this non-rod, non-cone photoreceptor might play an important role in human photoreception, this had yet to demonstrated unequivocally until now.

To address whether the cells identified in rodents and primates also exist in humans, Zaidi and colleagues first had to find patients who lacked functional rods and cones, but retained pRGCs--a formidable task, given that fewer than 5% of totally blind people are thought to retain this response.

This group of researchers was able to identify two such rare patients, allowing them to perform a series of complementary experiments to address whether non-visual responses are possible in the absence of rods and cones and to determine the most effective wavelength, or color, of light that induced a response. In the first patient, the effect of light on melatonin secretion was examined. Melatonin is a hormone produced at night that influences arousal and is secreted in a cyclic fashion. Just like sighted individuals, the blind patient exhibited acute suppression of melatonin in response to light and was most sensitive to blue-light exposure.

Furthermore, blue light also shifted the timing of the circadian pacemaker and improved alertness, as measured by subjective scales, auditory reaction time, and changes in brain activity. While a few rods and/or cones may remain, Zaidi and colleagues have strong evidence to show that they contribute little, if at all, to these effects. Thus the authors were able to show that the effects were maximal in response to wavelengths of light that the retinal ganglion cells respond best to, and not the wavelength that the visual system detects best.

In the second patient, a different a set of tests was administered to assess the effects of light. First, the pupil-constriction response to various wavelengths and intensities of light was examined. Consistent with the major role of the pRGCs in mediating this response, pupillary contriction was stimulated most by blue light (~480 nm), the wavelength that pRGCs are most stimulated by.

Given that the non-visual responses to light appeared to be intact in this patient, the researchers were prompted to ask whether some minimal awareness of light might still be retained despite the inability to detect any response to light by conventional measures and the patient's inability to see light. Remarkably, the patient was able to tell that the blue light, but not any other color, was switched on, demonstrating that the pRGCs also contribute to our ability to "see" light.

These results have a number of important implications for human vision and vision-related diseases. First, they suggest humans possess light-sensitive cells, apart from rods and cones, that are important for non-visual light responses such as the entrainment of circadian rhythms and elevating arousal and brain activity. Second, this information may change how injuries to the eye are treated.

For example, surgeons might want to think twice about removing a damaged eye that still possesses functioning pRGCs, given the important physiological role that these cells play in maintaining normally timed sleep. We will now need to begin to think about these additional functions of the human eye, and consider not just vision, but also how light affects sleep, alertness, performance, and human health. The remarkable discovery of a novel photoreceptor in the mammalian eye has shed new light on an organ that has been studied for thousands of years.
-end-
The researchers include Farhan H. Zaidi, Division of Neuroscience and Mental Health Faculty of Medicine, Imperial College London, London, UK; Joseph T. Hull, Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA, USA; Stuart N. Peirson, Nuffield Laboratory of Ophthalmology, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK; Katharina Wulff, Nuffield Laboratory of Ophthalmology, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK; Daniel Aeschbach, Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA, USA, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Joshua J. Gooley, Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA, USA, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; George C. Brainard, Department of Neurology, Thomas Jefferson University, Philadelphia, PA, USA; Kevin Gregory-Evans, Division of Neuroscience and Mental Health Faculty of Medicine, Imperial College London, London, UK; Joseph F. Rizzo III, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA; Charles A. Czeisler, Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA, USA, Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA; Russell G. Foster, Nuffield Laboratory of Ophthalmology, University of Oxford, Wellcome Trust Centre for Human Genetics, Oxford, UK; Merrick J. Moseley, Department of Optometry and Visual Science, City University, London, UK; and Steven W. Lockley, Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA, USA, and Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.

Cell Press

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