OAT Practice Test 14

A Third Kind of Photoreceptor

¹For more than a century, textbooks taught that the vertebrate eye detects light with just two kinds of photoreceptor cells. Rods, which are extremely sensitive, support vision in dim light, while cones, which come in several types tuned to different wavelengths, support color vision and fine detail in daylight. Both lie in the outermost layer of the retina, and the signals they generate pass through intermediate neurons to the retinal ganglion cells, whose long fibers form the optic nerve and carry visual information to the brain. In this picture, ganglion cells were relays, not detectors.

²Yet light does more than create images. It also resets the body's internal clock, a cluster of neurons in the hypothalamus called the suprachiasmatic nucleus, which coordinates daily rhythms of sleep, hormone release, and body temperature. Light also controls the size of the pupil. Researchers studying mice with inherited diseases that destroyed nearly all of their rods and cones made a puzzling observation: these animals, though unable to see in any ordinary sense, still adjusted their daily activity rhythms to a shifted cycle of light and dark, and their pupils still constricted in bright light. When the eyes were removed, these responses disappeared. Some photoreceptor in the eye, other than rods and cones, had to be responsible.

³The answer emerged around the turn of the twenty-first century. A light-sensitive pigment called melanopsin, first found in the skin of frogs, was detected in a very small subset of retinal ganglion cells, only a few percent of the total at most. Recordings showed that these cells responded to light even when all input from rods and cones was blocked with drugs, or when the cells were physically isolated from the rest of the retina. They were therefore named intrinsically photosensitive retinal ganglion cells. Mice engineered to lack melanopsin lost this intrinsic sensitivity, and mice lacking rods, cones, and melanopsin all at once lost their circadian and pupillary responses to light entirely.

⁴The responses of these cells differ markedly from those of rods and cones. Rods and cones react within milliseconds and adapt quickly, signaling changes and edges in the visual scene. Melanopsin-containing cells respond sluggishly, taking seconds to reach full activity, but they keep firing for as long as the light persists. They are also relatively insensitive, requiring fairly bright light. In short, they are poorly suited to forming images but well suited to measuring the overall level of illumination over minutes and hours, exactly the information a clock needs to judge whether it is day or night. Melanopsin is most sensitive to blue light with a wavelength near 480 nanometers, somewhat shorter than the wavelengths to which the main daylight cones are most sensitive.

⁵The fibers of these ganglion cells travel to the suprachiasmatic nucleus and to a region of the midbrain that controls the pupil, among other targets. The cells are not entirely independent of the rest of the retina: they also receive signals from rods and cones, which allow them to respond to dimmer light than melanopsin alone could detect. Under ordinary conditions the three systems work together, with melanopsin dominating the response to bright, prolonged light.

⁶The discovery has had clinical implications. Some people who are blind because their rods and cones have degenerated still show suppression of the nighttime hormone melatonin when exposed to bright light, and their daily rhythms can remain aligned with the solar day. Diseases that damage the ganglion cells themselves, by contrast, can disrupt these responses. Clinicians have begun to compare pupil responses to blue and red light as a way of assessing ganglion cell function, and some have argued that decisions about removing the eyes of blind patients should take the role of these cells into account.

⁷The findings have also shaped advice about artificial light. Because the clock is most sensitive to bright, blue-rich light, exposure in the evening can delay the body's internal timing and suppress melatonin. How much ordinary indoor lighting and electronic screens contribute to sleep problems is still debated, since such sources are usually far dimmer than daylight. What is no longer in doubt is that the eye serves two functions: it is an instrument for seeing, and it is also a light meter for the body's clock.