Intrinsically photosensitive retinal ganglion cell

Last updated
Overview of the retina photoreceptors. ipRGCs labelled at the top-right. Overview of the retina photoreceptors (a).png
Overview of the retina photoreceptors. ipRGCs labelled at the top-right.

Intrinsically photosensitive retinal ganglion cells (ipRGCs), also called photosensitive retinal ganglion cells (pRGC), or melanopsin-containing retinal ganglion cells (mRGCs), are a type of neuron in the retina of the mammalian eye. The presence of something like ipRGCs was first suspected in 1927 when rodless, coneless mice still responded to a light stimulus through pupil constriction; [1] this implied that rods and cones are not the only light-sensitive neurons in the retina. [2] Yet research on these cells did not advance until the 1980s. Recent research has shown that these retinal ganglion cells, unlike other retinal ganglion cells, are intrinsically photosensitive due to the presence of melanopsin, a light-sensitive protein. Therefore, they constitute a third class of photoreceptors, in addition to rod and cone cells. [3]

Contents

Overview

An ipRGC, shown here as a complied image of the retina from proximal inner nuclear layer to the ganglion cell layer with fluorescent labeling of melanopsin Melanopsin stain.jpg
An ipRGC, shown here as a complied image of the retina from proximal inner nuclear layer to the ganglion cell layer with fluorescent labeling of melanopsin
Spectral sensitivities of the photoreceptors in the human eye. Overview of the retina photoreceptors (b).png
Spectral sensitivities of the photoreceptors in the human eye.

Compared to the rods and cones, the ipRGCs respond more sluggishly and signal the presence of light over the long term. [5] They represent a very small subset (~1%) of the retinal ganglion cells. [6] Their functional roles are non-image-forming and fundamentally different from those of pattern vision; they provide a stable representation of ambient light intensity. They have at least three primary functions:

Photoreceptive ganglion cells have been isolated in humans, where, in addition to regulating the circadian rhythm, they have been shown to mediate a degree of light recognition in rodless, coneless subjects suffering with disorders of rod and cone photoreceptors. [9] Work by Farhan H. Zaidi and colleagues showed that photoreceptive ganglion cells may have some visual function in humans.

The photopigment of photoreceptive ganglion cells, melanopsin, is excited by light mainly in the blue portion of the visible spectrum (absorption peaks at ~480 nanometers [10] ). The phototransduction mechanism in these cells is not fully understood, but seems likely to resemble that in invertebrate rhabdomeric photoreceptors. In addition to responding directly to light, these cells may receive excitatory and inhibitory influences from rods and cones by way of synaptic connections in the retina.

The axons from these ganglia innervate regions of the brain related to object recognition, including the superior colliculus and dorsal lateral geniculate nucleus. [8]

Structure

ipRGC receptor

Melanopsin structure Melanopsin.png
Melanopsin structure

These photoreceptor cells project both throughout the retina and into the brain. They contain the photopigment melanopsin in varying quantities along the cell membrane, including on the axons up to the optic disc, the soma, and dendrites of the cell. [3] ipRGCs contain membrane receptors for the neurotransmitters glutamate, glycine, and GABA. [11] Photosensitive ganglion cells respond to light by depolarizing, thus increasing the rate at which they fire nerve impulses, which is opposite to that of other photoreceptor cells, which hyperpolarize in response to light. [12]

Results of studies in mice suggest that the axons of ipRGCs are unmyelinated. [3]

Melanopsin

Unlike other photoreceptor pigments, melanopsin has the ability to act as both the excitable photopigment and as a photoisomerase. Unlike the visual opsins in rod cells and cone cells, which rely on the standard visual cycles for recharging all-trans-retinal back into the photosensitive 11-cis-retinal, melanopsin is able to isomerize all-trans-retinal into 11-cis-retinal itself when stimulated with another photon. [11] An ipRGC therefore does not rely on Müller cells and/or retinal pigment epithelium cells for this conversion.

The two isoforms of melanopsin differ in their spectral sensitivity, for the 11-cis-retinal isoform is more responsive to shorter wavelengths of light, while the all-trans isoform is more responsive to longer wavelengths of light. [13]

Synaptic inputs and outputs

Synaptic inputs and outputs of ipRGCs and their corresponding location in the brain Diagram of inputs and outputs of ipRGC 1.jpg
Synaptic inputs and outputs of ipRGCs and their corresponding location in the brain

Inputs

ipRGCs are both pre- and postsynaptic to dopaminergic amacrine cells (DA cells) via reciprocal synapses, with ipRGCs sending excitatory signals to the DA cells, and the DA cells sending inhibitory signals to the ipRGCs. These inhibitory signals are mediated through GABA, which is co-released from the DA cells along with dopamine. Dopamine has functions in the light-adaptation process by up-regulating melanopsin transcription in ipRGCs and thus increasing the photoreceptor's sensitivity. [3] In parallel with the DA amacrine cell inhibition, somatostatin-releasing amacrine cells, themselves inhibited by DA amacrine cells, inhibit ipRGCs. [14] Other synaptic inputs to ipRGC dendrites include cone bipolar cells and rod bipolar cells. [11]

Outputs

One postsynaptic target of ipRGCs is the suprachiasmatic nucleus (SCN) of the hypothalamus, which serves as the circadian clock in an organism. ipRGCs release both pituitary adenylyl cyclase-activating protein (PACAP) and glutamate onto the SCN via a monosynaptic connection called the retinohypothalamic tract (RHT). [15] Glutamate has an excitatory effect on SCN neurons, and PACAP appears to enhance the effects of glutamate in the hypothalamus. [16]

Other post synaptic targets of ipRGCs include: the intergenticulate leaflet (IGL), a cluster of neurons located in the thalamus, which play a role in circadian entrainment; the olivary pretectal nucleus (OPN), a cluster of neurons in the midbrain that controls the pupillary light reflex; the ventrolateral preoptic nucleus (VLPO), located in the hypothalamus and is a control center for sleep; as well as to[ clarify ] the amygdala. [3]

Function

Pupillary light reflex

Inputs and outputs to ipRGCs involved in the pupillary light reflex IpRGC PLR.svg
Inputs and outputs to ipRGCs involved in the pupillary light reflex

Using various photoreceptor knockout mice, researchers have identified the role of ipRGCs in both the transient and sustained signaling of the pupillary light reflex (PLR). [17] Transient PLR occurs at dim to moderate light intensities and is a result of phototransduction occurring in rod cells, which provide synaptic input onto ipRGCs, which in turn relay the information to the olivary pretectal nucleus in the midbrain. [18] The neurotransmitter involved in the relay of information to the midbrain from the ipRGCs in the transient PLR is glutamate. At brighter light intensities the sustained PLR occurs, which involves both phototransduction of the rod providing input to the ipRGCs and phototransduction of the ipRGCs themselves via melanopsin. Researchers have suggested that the role of melanopsin in the sustained PLR is due to its lack of adaptation to light stimuli in contrast to rod cells, which exhibit adaptation. The sustained PLR is maintained by PACAP release from ipRGCs in a pulsatile manner. [17]

Possible role in conscious sight

Experiments with rodless, coneless humans allowed another possible role for the receptor to be studied. In 2007, a new role was found for the photoreceptive ganglion cell. Zaidi and colleagues showed that in humans the retinal ganglion cell photoreceptor contributes to conscious sight as well as to non-image-forming functions like circadian rhythms, behaviour and pupillary reactions. [9] Since these cells respond mostly to blue light, it has been suggested that they have a role in mesopic vision [ citation needed ] and that the old theory of a purely duplex retina with rod (dark) and cone (light) light vision was simplistic. Zaidi and colleagues' work with rodless, coneless human subjects hence has also opened the door into image-forming (visual) roles for the ganglion cell photoreceptor.

The discovery that there are parallel pathways for vision was made: one classic rod- and cone-based arising from the outer retina, the other a rudimentary visual brightness detector arising from the inner retina. The latter seems to be activated by light before the former. [9] Classic photoreceptors also feed into the novel photoreceptor system, and colour constancy may be an important role as suggested by Foster[ citation needed ].

It has been suggested by the authors of the rodless, coneless human model that the receptor could be instrumental in understanding many diseases, including major causes of blindness worldwide such as glaucoma, a disease which affects ganglion cells.

In other mammals, photosensitive ganglia have proven to have a genuine role in conscious vision. Tests conducted by Jennifer Ecker et al. found that rats lacking rods and cones were able to learn to swim toward sequences of vertical bars rather than an equally luminescent gray screen. [8]

Violet-to-blue light

Most work suggests that the peak spectral sensitivity of the receptor is between 460 and 484 nm. Lockley et al. in 2003 [19] showed that 460 nm (blue) wavelengths of light suppress melatonin twice as much as 555 nm (green) light, the peak sensitivity of the photopic visual system. In work by Zaidi, Lockley and co-authors using a rodless, coneless human, it was found that a very intense 481 nm stimulus led to some conscious light perception, meaning that some rudimentary vision was realized. [9]

Discovery

In 1923, Clyde E. Keeler observed that the pupils in the eyes of blind mice he had accidentally bred still responded to light. [2] The ability of the rodless, coneless mice to retain a pupillary light reflex was suggestive of an additional photoreceptor cell. [11]

In the 1980s, research in rod- and cone-deficient rats showed regulation of dopamine in the retina, a known neuromodulator for light adaptation and photoentrainment. [3]

Research continued in 1991, when Russell G. Foster and colleagues, including Ignacio Provencio, showed that rods and cones were not necessary for photoentrainment, the visual drive of the circadian rhythm, nor for the regulation of melatonin secretion from the pineal gland, via rod- and cone-knockout mice. [20] [11] Later work by Provencio and colleagues showed that this photoresponse was mediated by the photopigment melanopsin, present in the ganglion cell layer of the retina. [21]

The photoreceptors were identified in 2002 by Samer Hattar, David Berson and colleagues, where they were shown to be melanopsin expressing ganglion cells that possessed an intrinsic light response and projected to a number of brain areas involved in non-image-forming vision. [22] [23]

In 2005, Panda, Melyan, Qiu, and colleagues demonstrated that the melanopsin photopigment was the phototransduction pigment in ganglion cells. [24] [25] Dennis Dacey and colleagues showed in a species of Old World monkey that giant ganglion cells expressing melanopsin projected to the lateral geniculate nucleus (LGN). [26] [6] Previously only projections to the midbrain (pre-tectal nucleus) and hypothalamus (supra-chiasmatic nuclei, SCN) had been shown. However, a visual role for the receptor was still unsuspected and unproven.

Research

Research in humans

Attempts were made to hunt down the receptor in humans, but humans posed special challenges and demanded a new model. Unlike in other animals, researchers could not ethically induce rod and cone loss either genetically or with chemicals so as to directly study the ganglion cells. For many years, only inferences could be drawn about the receptor in humans, though these were at times pertinent.

In 2007, Zaidi and colleagues published their work on rodless, coneless humans, showing that these people retain normal responses to nonvisual effects of light. [9] [27] The identity of the non-rod, non-cone photoreceptor in humans was found to be a ganglion cell in the inner retina as shown previously in rodless, coneless models in some other mammals. The work was done using patients with rare diseases that wiped out classic rod and cone photoreceptor function but preserved ganglion cell function. [9] [27] Despite having no rods or cones, the patients continued to exhibit circadian photoentrainment, circadian behavioural patterns, melatonin suppression, and pupil reactions, with peak spectral sensitivities to environmental and experimental light that match the melanopsin photopigment. Their brains could also associate vision with light of this frequency. Clinicians and scientists are now seeking to understand the new receptor's role in human diseases and blindness.[ citation needed ] Intrinsically photosensitive RGCs have also been implicated in the exacerbation of headache by light during migraine attacks. [28]

See also

Related Research Articles

Free-running sleep is a rare sleep pattern whereby the sleep schedule of a person shifts later every day. It occurs as the sleep disorder non-24-hour sleep–wake disorder or artificially as part of experiments used in the study of circadian and other rhythms in biology. Study subjects are shielded from all time cues, often by a constant light protocol, by a constant dark protocol or by the use of light/dark conditions to which the organism cannot entrain such as the ultrashort protocol of one hour dark and two hours light. Also, limited amounts of food may be made available at short intervals so as to avoid entrainment to mealtimes. Subjects are thus forced to live by their internal circadian "clocks".

<span class="mw-page-title-main">Retina</span> Part of the eye

The retina is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then processes that image within the retina and sends nerve impulses along the optic nerve to the visual cortex to create visual perception. The retina serves a function which is in many ways analogous to that of the film or image sensor in a camera.

<span class="mw-page-title-main">Chronobiology</span> Field of biology

Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος, and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.

<span class="mw-page-title-main">Visual system</span> Body parts responsible for vision

The visual system is the physiological basis of visual perception. The system detects, transduces and interprets information concerning light within the visible range to construct an image and build a mental model of the surrounding environment. The visual system is associated with the eye and functionally divided into the optical system and the neural system.

<span class="mw-page-title-main">Photoreceptor cell</span> Type of neuroepithelial cell

A photoreceptor cell is a specialized type of neuroepithelial cell found in the retina that is capable of visual phototransduction. The great biological importance of photoreceptors is that they convert light into signals that can stimulate biological processes. To be more specific, photoreceptor proteins in the cell absorb photons, triggering a change in the cell's membrane potential.

<span class="mw-page-title-main">Cone cell</span> Photoreceptor cells responsible for color vision made to function in bright light

Cone cells or cones are photoreceptor cells in the retinas of vertebrates' eyes. They respond differently to light of different wavelengths, and the combination of their responses is responsible for color vision. Cones function best in relatively bright light, called the photopic region, as opposed to rod cells, which work better in dim light, or the scotopic region. Cone cells are densely packed in the fovea centralis, a 0.3 mm diameter rod-free area with very thin, densely packed cones which quickly reduce in number towards the periphery of the retina. Conversely, they are absent from the optic disc, contributing to the blind spot. There are about six to seven million cones in a human eye, with the highest concentration being towards the macula.

In visual physiology, adaptation is the ability of the retina of the eye to adjust to various levels of light. Natural night vision, or scotopic vision, is the ability to see under low-light conditions. In humans, rod cells are exclusively responsible for night vision as cone cells are only able to function at higher illumination levels. Night vision is of lower quality than day vision because it is limited in resolution and colors cannot be discerned; only shades of gray are seen. In order for humans to transition from day to night vision they must undergo a dark adaptation period of up to two hours in which each eye adjusts from a high to a low luminescence "setting", increasing sensitivity hugely, by many orders of magnitude. This adaptation period is different between rod and cone cells and results from the regeneration of photopigments to increase retinal sensitivity. Light adaptation, in contrast, works very quickly, within seconds.

<span class="mw-page-title-main">Retinal ganglion cell</span> Type of cell within the eye

A retinal ganglion cell (RGC) is a type of neuron located near the inner surface of the retina of the eye. It receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain.

<span class="mw-page-title-main">Melanopsin</span> Mammalian protein found in Homo sapiens

Melanopsin is a type of photopigment belonging to a larger family of light-sensitive retinal proteins called opsins and encoded by the gene Opn4. In the mammalian retina, there are two additional categories of opsins, both involved in the formation of visual images: rhodopsin and photopsin in the rod and cone photoreceptor cells, respectively.

<span class="mw-page-title-main">Giant retinal ganglion cells</span>

Giant retinal ganglion cells are photosensitive ganglion cells with large dendritic trees discovered in the human and macaque retina by Dacey et al. (2005).

<span class="mw-page-title-main">Retinohypothalamic tract</span> Neural pathway involved with circadian rhythms

In neuroanatomy, the retinohypothalamic tract (RHT) is a photic neural input pathway involved in the circadian rhythms of mammals. The origin of the retinohypothalamic tract is the intrinsically photosensitive retinal ganglion cells (ipRGC), which contain the photopigment melanopsin. The axons of the ipRGCs belonging to the retinohypothalamic tract project directly, monosynaptically, to the suprachiasmatic nuclei (SCN) via the optic nerve and the optic chiasm. The suprachiasmatic nuclei receive and interpret information on environmental light, dark and day length, important in the entrainment of the "body clock". They can coordinate peripheral "clocks" and direct the pineal gland to secrete the hormone melatonin.

Ignacio Provencio is an American neuroscientist and the discoverer of melanopsin, an opsin found in specialized photosensitive ganglion cells of the mammalian retina. Provencio served as the program committee chair of the Society for Research on Biological Rhythms from 2008 to 2010.

Photoreceptor proteins are light-sensitive proteins involved in the sensing and response to light in a variety of organisms. Some examples are rhodopsin in the photoreceptor cells of the vertebrate retina, phytochrome in plants, and bacteriorhodopsin and bacteriophytochromes in some bacteria. They mediate light responses as varied as visual perception, phototropism and phototaxis, as well as responses to light-dark cycles such as circadian rhythm and other photoperiodisms including control of flowering times in plants and mating seasons in animals.

The visual cycle is a process in the retina that replenishes the molecule retinal for its use in vision. Retinal is the chromophore of most visual opsins, meaning it captures the photons to begin the phototransduction cascade. When the photon is absorbed, the 11-cis retinal photoisomerizes into all-trans retinal as it is ejected from the opsin protein. Each molecule of retinal must travel from the photoreceptor cell to the RPE and back in order to be refreshed and combined with another opsin. This closed enzymatic pathway of 11-cis retinal is sometimes called Wald's visual cycle after George Wald (1906–1997), who received the Nobel Prize in 1967 for his work towards its discovery.

Light effects on circadian rhythm are the effects that light has on circadian rhythm.

<span class="mw-page-title-main">Mammalian eye</span>

Mammals normally have a pair of eyes. Although mammalian vision is not so excellent as bird vision, it is at least dichromatic for most of mammalian species, with certain families possessing a trichromatic color perception.

<span class="mw-page-title-main">Russell Foster</span>

Russell Grant Foster, CBE, FRS FMedSci is a British professor of circadian neuroscience, the Director of the Nuffield Laboratory of Ophthalmology and the Head of the Sleep and Circadian Neuroscience Institute (SCNi). He is also a Nicholas Kurti Senior Fellow at Brasenose College at the University of Oxford. Foster and his group are credited with key contributions to the discovery of the non-rod, non-cone, photosensitive retinal ganglion cells (pRGCs) in the mammalian retina which provide input to the circadian rhythm system. He has written and co-authored over a hundred scientific publications.

<span class="mw-page-title-main">King-Wai Yau</span> Chinese-American neuroscientist

King-Wai Yau is a Chinese-born American neuroscientist and Professor of Neuroscience at Johns Hopkins University School of Medicine in Baltimore, Maryland.

Samer Hattar is a chronobiologist and a leader in the field of non-image forming photoreception. He is the Chief of the Section on Light and Circadian Rhythms at the National Institute of Mental Health, part of the National Institutes of Health. He was previously an associate professor in the Department of Neuroscience and the Department of Biology at Johns Hopkins University in Baltimore, MD. He is best known for his investigation into the role of melanopsin and intrinsically photosensitive retinal ganglion cells (ipRGC) in the entrainment of circadian rhythms.

Tiffany M. Schmidt is an American researcher and chronobiologist, currently working as an associate professor of Neurobiology at Northwestern University. Schmidt, who works in Evanston, Illinois, studies the role of retinal ganglion cells (RGC) to determine how light can affect behavior, hormonal changes, vision, sleep, and circadian entrainment.

References

  1. ↑ Keeler, Clyde E. (1927). "Iris movements in blind mice". American Journal of Physiology. 81 (1): 107–112. doi:10.1152/ajplegacy.1927.81.1.107.
  2. 1 2 Keeler CE (October 1928). "Blind Mice". Journal of Experimental Zoology. 51 (4): 495–508. doi:10.1002/jez.1400510404.
  3. 1 2 3 4 5 6 Do MT, Yau KW (October 2010). "Intrinsically photosensitive retinal ganglion cells". Physiological Reviews. 90 (4): 1547–81. doi:10.1152/physrev.00013.2010. PMC   4374737 . PMID   20959623.
  4. ↑ Blume C, Garbazza C, Spitschan M (2019). "Effects of light on human circadian rhythms, sleep and mood". Somnologie (Berl). 23 (3): 147–156. doi:10.1007/s11818-019-00215-x. PMC   6751071 . PMID   31534436.
  5. ↑ Wong KY, Dunn FA, Berson DM (December 2005). "Photoreceptor adaptation in intrinsically photosensitive retinal ganglion cells". Neuron. 48 (6): 1001–10. doi: 10.1016/j.neuron.2005.11.016 . PMID   16364903.
  6. 1 2 Berson DM (June 2003). "Strange vision: ganglion cells as circadian photoreceptors". Trends in Neurosciences. 26 (6): 314–20. doi:10.1016/S0166-2236(03)00130-9. PMID   12798601. S2CID   15149809.
  7. ↑ Fan SM, Chang YT, Chen CL, Wang WH, Pan MK, Chen WP, et al. (July 2018). "External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway". Proceedings of the National Academy of Sciences of the United States of America. 115 (29): E6880–E6889. Bibcode:2018PNAS..115E6880F. doi: 10.1073/pnas.1719548115 . PMC   6055137 . PMID   29959210.
  8. 1 2 3 4 5 Ecker JL, Dumitrescu ON, Wong KY, Alam NM, Chen SK, LeGates T, et al. (July 2010). "Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision". Neuron. 67 (1): 49–60. doi:10.1016/j.neuron.2010.05.023. PMC   2904318 . PMID   20624591.
  9. 1 2 3 4 5 6 Zaidi FH, Hull JT, Peirson SN, Wulff K, Aeschbach D, Gooley JJ, et al. (December 2007). "Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an outer retina". Current Biology. 17 (24): 2122–8. doi:10.1016/j.cub.2007.11.034. PMC   2151130 . PMID   18082405.
  10. ↑ Berson DM (August 2007). "Phototransduction in ganglion-cell photoreceptors". Pflügers Archiv. 454 (5): 849–55. doi: 10.1007/s00424-007-0242-2 . PMID   17351786.
  11. 1 2 3 4 5 Kolb H, Fernandez E, Nelson R (1995-01-01). "Melanopsin-expressing, Intrinsically Photosensitive Retinal Ganglion Cells (IpRGCs)". In Kolb H, Fernandez E, Nelson R (eds.). Webvision: The Organization of the Retina and Visual System. University of Utah Health Sciences Center. PMID   21413389.
  12. ↑ Do MT, Kang SH, Xue T, Zhong H, Liao HW, Bergles DE, Yau KW (January 2009). "Photon capture and signalling by melanopsin retinal ganglion cells". Nature. 457 (7227): 281–7. Bibcode:2009Natur.457..281D. doi:10.1038/nature07682. PMC   2794210 . PMID   19118382.
  13. ↑ Chellappa SL, Ly JQ, Meyer C, Balteau E, Degueldre C, Luxen A, et al. (April 2014). "Photic memory for executive brain responses". Proceedings of the National Academy of Sciences of the United States of America. 111 (16): 6087–91. Bibcode:2014PNAS..111.6087C. doi: 10.1073/pnas.1320005111 . PMC   4000819 . PMID   24616488.
  14. ↑ Vuong HE, Hardi CN, Barnes S, Brecha NC (December 2015). "Parallel Inhibition of Dopamine Amacrine Cells and Intrinsically Photosensitive Retinal Ganglion Cells in a Non-Image-Forming Visual Circuit of the Mouse Retina". The Journal of Neuroscience. 35 (48): 15955–70. doi:10.1523/jneurosci.3382-15.2015. PMC   4666919 . PMID   26631476.
  15. ↑ Colwell CS, Michel S, Itri J, Rodriguez W, Tam J, Lelièvre V, et al. (November 2004). "Selective deficits in the circadian light response in mice lacking PACAP". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 287 (5): R1194-201. doi:10.1152/ajpregu.00268.2004. PMID   15217792.
  16. ↑ Butcher GQ, Lee B, Cheng HY, Obrietan K (June 2005). "Light stimulates MSK1 activation in the suprachiasmatic nucleus via a PACAP-ERK/MAP kinase-dependent mechanism". The Journal of Neuroscience. 25 (22): 5305–13. doi:10.1523/jneurosci.4361-04.2005. PMC   6724997 . PMID   15930378.
  17. 1 2 Keenan WT, Rupp AC, Ross RA, Somasundaram P, Hiriyanna S, Wu Z, et al. (September 2016). "A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction". eLife. 5. doi: 10.7554/eLife.15392 . PMC   5079752 . PMID   27669145.
  18. ↑ Gamlin PD, McDougal DH, Pokorny J, Smith VC, Yau KW, Dacey DM (March 2007). "Human and macaque pupil responses driven by melanopsin-containing retinal ganglion cells". Vision Research. 47 (7): 946–54. doi:10.1016/j.visres.2006.12.015. PMC   1945238 . PMID   17320141.
  19. ↑ Lockley SW, Brainard GC, Czeisler CA (September 2003). "High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light". The Journal of Clinical Endocrinology and Metabolism. 88 (9): 4502–5. doi: 10.1210/jc.2003-030570 . PMID   12970330.
  20. ↑ Foster RG, Provencio I, Hudson D, Fiske S, De Grip W, Menaker M (July 1991). "Circadian photoreception in the retinally degenerate mouse (rd/rd)". Journal of Comparative Physiology A: Sensory, Neural, and Behavioral Physiology. 169 (1): 39–50. doi:10.1007/BF00198171. PMID   1941717. S2CID   1124159.
  21. ↑ Provencio I, Rodriguez IR, Jiang G, Hayes WP, Moreira EF, Rollag MD (January 2000). "A novel human opsin in the inner retina". The Journal of Neuroscience. 20 (2): 600–5. doi:10.1523/jneurosci.20-02-00600.2000. PMC   6772411 . PMID   10632589.
  22. ↑ Berson DM, Dunn FA, Takao M (February 2002). "Phototransduction by retinal ganglion cells that set the circadian clock". Science. 295 (5557): 1070–3. Bibcode:2002Sci...295.1070B. doi:10.1126/science.1067262. PMID   11834835. S2CID   30745140.
  23. ↑ Hattar S, Liao HW, Takao M, Berson DM, Yau KW (February 2002). "Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity". Science. 295 (5557): 1065–70. Bibcode:2002Sci...295.1065H. doi:10.1126/science.1069609. PMC   2885915 . PMID   11834834.
  24. ↑ Panda S, Nayak SK, Campo B, Walker JR, Hogenesch JB, Jegla T (January 2005). "Illumination of the melanopsin signaling pathway". Science. 307 (5709): 600–4. Bibcode:2005Sci...307..600P. doi:10.1126/science.1105121. PMID   15681390. S2CID   22713904.
  25. ↑ Qiu X, Kumbalasiri T, Carlson SM, Wong KY, Krishna V, Provencio I, Berson DM (February 2005). "Induction of photosensitivity by heterologous expression of melanopsin". Nature. 433 (7027): 745–9. Bibcode:2005Natur.433..745Q. doi:10.1038/nature03345. PMID   15674243. S2CID   24999816.
  26. ↑ Dacey DM, Liao HW, Peterson BB, Robinson FR, Smith VC, Pokorny J, et al. (February 2005). "Melanopsin-expressing ganglion cells in primate retina signal colour and irradiance and project to the LGN". Nature. 433 (7027): 749–54. Bibcode:2005Natur.433..749D. doi:10.1038/nature03387. PMID   15716953. S2CID   4401722.
  27. 1 2 Coghlan A (2007). "How blind people see sunrise and sunset". New Scientist. 196 (2635–2636): 9. doi:10.1016/S0262-4079(07)63172-8.
  28. ↑ Noseda R (2010). "A neural mechanism for exacerbation of headache by light". Nature Neuroscience. 13 (2): 239–245. doi:10.1038/nn.2475. PMC   2818758 . PMID   20062053.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.