Intrinsically photosensitive retinal ganglion cell

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, This implied that rods and cones are not the only light-sensitive neurons in the retina. 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. Compared to the rods and cones, the ipRGCs respond more sluggishly and signal the presence of light over the long term. They represent a very small subset (~1%) of the retinal ganglion cells. 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: They play a major role in synchronizing circadian rhythms to the 24-hour light/dark cycle, providing primarily length-of-day and length-of-night information. They send light information via the retinohypothalamic tract (RHT) directly to the circadian pacemaker of the brain, the suprachiasmatic nucleus of the hypothalamus. The physiological properties of these ganglion cells match known properties of the daily light entrainment (synchronization) mechanism regulating circadian rhythms. In addition, ipRGCs could also influence peripheral tissues such as the hair follicle regeneration through SCN-sympathetic nerve circuit. Photosensitive ganglion cells innervate other brain targets, such as the center of pupillary control, the olivary pretectal nucleus of the midbrain.

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Entrainment (chronobiology)

In the study of chronobiology, entrainment occurs when rhythmic physiological or behavioral events match their period to that of an environmental oscillation. It is ultimately the interaction between circadian rhythms and the environment. A central example is the entrainment of circadian rhythms to the daily light–dark cycle, which ultimately is determined by the Earth's rotation. Exposure to certain environmental stimuli will cue a phase shift, and abrupt change in the timing of the rhythm.

Retinohypothalamic tract

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.

Retinal ganglion cell

A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (the ganglion cell layer) 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.

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Comparison of acute non-visual bright light responses in patients with optic nerve disease, glaucoma and healthy controls

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This study examined the effect of optic nerve disease, hence retinal ganglion cell loss, on nonvisual functions related to melanopsin signalling. Test subjects were patients with bilateral visual loss and optic atrophy from either hereditary optic neuropathy (n = 11) or glaucoma (n = 11). We measured melatonin suppression, subjective sleepiness and cognitive functions in response to bright light exposure in the evening. We also quantified the post-illumination pupil response to a blue light stimulus. All results were compared to age-matched controls (n = 22). Both groups of patients showed similar melatonin suppression when compared to their controls. Greater melatonin suppression was intra-individually correlated to larger post-illumination pupil response in patients and controls. Only the glaucoma patients demonstrated a relative attenuation of their pupil response. In addition, they were sleepier with slower reaction times during nocturnal light exposure. In conclusion, glaucomatous, but not hereditary, optic neuropathy is associated with reduced acute light effects. At mild to moderate stages of disease, this is detected only in the pupil function and not in responses conveyed via the retinohypothalamic tract such as melatonin suppression.

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PURPOSE. Nonvisual light-dependent functions in humans are conveyed mainly by intrinsically photosensitive retinal ganglion cells, which express melanopsin as photopigment. We aimed to identify the effects of circadian phase and sleepiness across 24 hours on various aspects of the pupil response to light stimulation. METHODS. We tested 10 healthy adults hourly in two 12-hour sessions covering a 24-hour period. Pupil responses to narrow bandwidth red (635 +/- 18 nm) and blue (463 +/- 24 nm) light (duration of 1 and 30 seconds) at equal photon fluxes were recorded, and correlated with salivary melatonin concentrations at the same circadian phases and to subjective sleepiness ratings. The magnitude of pupil constriction was determined from minimal pupil size. The post-stimulus pupil response was assessed from the pupil size at 6 seconds following light offset, the area within the redilation curve, and the exponential rate of redilation. RESULTS. Among the measured parameters, the pupil size 6 seconds after light offset correlated with melatonin concentrations (P < 0.05) and showed a significant modulation over 24 hours with maximal values after the nocturnal peak of melatonin secretion. In contrast, the post-stimulus pupil response following red light stimulation correlated with subjective sleepiness (P < 0.05) without significant changes over 24 hours. CONCLUSIONS. The post-stimulus pupil response to blue light as a marker of intrinsic melanopsin activity demonstrated a circadian modulation. In contrast, the effect of sleepiness was more apparent in the cone contribution to the pupil response. Thus, pupillary responsiveness to light is under influence of the endogenous circadian clock and subjective sleepiness. (Invest Ophthalmol Vis Sci. 2012;53:4546-4555) DOI: 10.1167/iovs.12-9494

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