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Retinal Ganglion Cells and Melanopsin

R. Soca MD | 11 February, 2021


          
            Retinal Ganglion Cells and Melanopsin

For many of us that went to school more than 20 years ago biology classes used to relatively simple; the retina was populated by two types of cells: the cones and rods. In recent years, our knowledge about retinal cells has exploded and significant attention is being devoted to a special group of cell called the Retinal ganglion cells. Retinal ganglion cells have a special pigment called melanopsin that is very important for circadian rhythms and the circadian system. When we look at the number of cells, retinal rods are by far the most common ones with more than 90 million rods per human retina; there are approximately 5 million retinal cones, and only 1 million retinal ganglion cells.

Not all retinal ganglion cells are involved in the control of the circadian system; some populations of ganglion cells have functions related to our perception of movement or changes in the intensity of light. For obvious reasons, our focus will be on the sleep and circadian functions of the retinal ganglion cells as well as the photopigment melanopsin.

In humans, there is a wide variety of retinal ganglion cells that can be classified using different criteria. Based on size, there are three main families:

  1. W-ganglion or small
  2. X-ganglion or medium
  3. Y- ganglion largest (these cells represent only a small percentage of the cells)

There are other classification systems that are based on the function of the cells or the projections of those cells but it is difficult to describe all the functions and characteristics of the entire retinal ganglion cell population with a single system. Cells that are relevant for the circadian system are classified as “photosensitive” cells because they react to light (not all ganglion cells react to light). The ability to react to light comes from a pigment called melanopsin.

Melanopsin is a photopigment belonging to a large family of light-sensitive retinal proteins called opsins. Opsins are proteins that react to light. Melanopsin was first discovered in skin cells in frogs in 1998, soon after its initial discovery, melanopsin was identified in retinal cells of blind mice that were able to follow a circadian pattern. The discovery of melanopsin showed that animals that are unable to “see” light were still able to follow a 24hour pattern and were getting some signal about the light/dark cycle.

Melanopsin is G-protein coupled receptor. The melanopsin protein has seven alpha helices integrated in the plasma membrane. The sensitivity of melanopsin is not the same for all forms of light. Laboratory studies have shown that melanopsin is most sensitive to light with a wavelength of 479 nm, this corresponds to the blue range of the visible light spectrum.

Current research shows that when retinal ganglion cells get exposed to blue light in the evening, these cells are able to block the production of melatonin by the pineal gland. We know that light in the morning tends to be rich in the blue side of the spectrum and it can affect the circadian system but we do not know the exact mechanisms or pathways associated with receiving blue light in the morning and then controlling the production of melatonin in the evening (i.e., where is this information stored during the day?).

As we mentioned earlier in this article, blue light is very activating for the retinal ganglion cells but these are not the only cells that are sensitive to this portion of the visual spectrum. Cones, a different type of cell, are also very sensitive to blue light; there are three types of cones and one in particular, the S-Cones, are also called “blue cones” due to their sensitivity to blue-colored light. Science has known for years that retinal cones were very important in the generation of images. There is still some debate as to whether retinal cones, in particular the blue ones, also contribute to the regulation of the circadian system or not.

References:

  • Watson AB (June 2014). "A formula for human retinal ganglion cell receptive field density as a function of visual field location"(PDF). Journal of Vision. 14 (7): 15. doi:10.1167/14.7.15. PMID 24982468.
  • Curcio CA, Sloan KR, Kalina RE, Hendrickson AE (February 1990). "Human photoreceptor topography" (PDF). The Journal of Comparative Neurology. 292 (4): 497–523. doi:10.1002/cne.902920402. PMID 2324310. S2CID 24649779.
  • Freedman MS, Lucas RJ, Soni B, von Schantz M, Muñoz M, David-Gray Z, Foster R (April 1999). "Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors". Science. 284 (5413): 502–4. Bibcode:1999Sci...284..502F. doi:10.1126/science.284.5413.502. PMID 10205061.
  • Bailes HJ, Lucas RJ (May 2013). "Human melanopsin forms a pigment maximally sensitive to blue light (λmax ≈ 479 nm) supporting activation of G(q/11) and G(i/o) signalling cascades". Proceedings. Biological Sciences. 280 (1759): 20122987. doi:10.1098/rspb.2012.2987. PMC 3619500. PMID 23554393.

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