Intrinsically Photosensitive (Melanopsin) Retinal Ganglion Cell Function in Glaucoma

Feigl, Beatrix; Mattes, Dietmar; Thomas, Ravi; Zele, Andrew J.

doi:10.1167/iovs.10-7069

Cited by 158 publications

(237 citation statements)

References 30 publications

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“…106,108 Dysfunction of ipRGCs in animal models of glaucoma have been corroborated by human studies because glaucoma patients with sleep disorders showed a reduction in the pupillary light response and suppression of nocturnal melatonin by light. [113][114][115][116][117][118] The potential role of ipRGCs has been described in other pathological processes. Concurrent regression of embryonic hyaloid vasculature and formation of the retinal vasculature occur postnatally in the mouse, 119 and the light response pathway that regulates both processes involves melanopsin.…”

mentioning

confidence: 99%

The retinal clock in mammals: role in health and disease

Felder-Schmittbuhl¹,

Calligaro²,

Dkhissi-Benyahya³

2017

CPT

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Abstract:The mammalian retina contains an extraordinary diversity of cell types that are highly organized into precise circuits to perceive and process visual information in a dynamic manner and transmit it to the brain. Above this builds up another level of complex dynamic, orchestrated by a circadian clock located within the retina, which allows retinal physiology, and hence visual function, to adapt to daily changes in light intensity. The mammalian retina is a remarkable model of circadian clock because it harbors photoreception, self-sustained oscillator function, and physiological outputs within the same tissue. However, the location of the retinal clock in mammals has been a matter of long debate. Current data have shown that clock properties are widely distributed among retinal cells and that the retina is composed of a network of circadian clocks located within distinct cellular layers. Nevertheless, the identity of the major pacemaker, if any, still warrants identification. In addition, the retina coordinates rhythmic behavior by providing visual input to the master hypothalamic circadian clock in the suprachiasmatic nuclei (SCN). This light entrainment of the SCN to the light/dark cycle involves a network of retinal photoreceptor cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). Although it was considered that these photoreceptors synchronized both retinal and SCN clocks, new data challenge this view, suggesting that none of these photoreceptors is involved in photic entrainment of the retinal clock. Because circadian organization is a ubiquitous feature of the retina and controls fundamental processes, the coherence from cell to tissue is critical for circadian functions, and disruption of retinal clock organization or its response to light can potentially have a major impact on retinal pathophysiology and vision.

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mentioning

confidence: 99%

The retinal clock in mammals: role in health and disease

Felder-Schmittbuhl¹,

Calligaro²,

Dkhissi-Benyahya³

2017

CPT

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show abstract

“…In a model of inherited glaucoma (mouse strain DBA/2J) in which IOP is elevated, melanopsin-expressing RGCs are not selectively spared (Jakobs et al 2005). Patients with early-stage glaucoma show no deficits in ipRGC function determined by the postillumination pupil response whereas in people with advanced glaucoma, ipRGC function was reduced (Feigl et al 2011). Conversely, axotomized melanopsin-expressing RGCs show enhanced survival compared to conventional RGCs in the mouse (Robinson and Madison 2004).…”

mentioning

confidence: 99%

Intrinsically photosensitive retinal ganglion cells

Pickard

Sollars

2010

Sci. China Life Sci.

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Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond to light in the absence of all rod and cone photoreceptor input. The existence of these ganglion cell photoreceptors, although predicted from observations scattered over many decades, was not established until it was shown that a novel photopigment, melanopsin, was expressed in retinal ganglion cells of rodents and primates. Phototransduction in mammalian ipRGCs more closely resembles that of invertebrate than vertebrate photoreceptors and appears to be mediated by transient receptor potential channels. In the retina, ipRGCs provide excitatory drive to dopaminergic amacrine cells and ipRGCs are coupled to GABAergic amacrine cells via gap junctions. Several subtypes of ipRGC have been identified in rodents based on their morphology, physiology and expression of molecular markers. ipRGCs convey irradiance information centrally via the optic nerve to influence several functions including photoentrainment of the biological clock located in the hypothalamus, the pupillary light reflex, sleep and perhaps some aspects of vision. In addition, ipRGCs may also contribute irradiance signals that interface directly with the autonomic nervous system to regulate rhythmic gene activity in major organs of the body. Here we review the early work that provided the motivation for searching for a new mammalian photoreceptor, the ground-breaking discoveries, current progress that continues to reveal the unusual properties of these neuron photoreceptors, and directions for future investigation.Keywords: Melanopsin, Circadian rhythms, Suprachiasmatic nucleus, Retina digitalcommons.unl.edu P i c k a r d & S o l l a r S i n R e v P h y s i o l B i o c h e m P h a R m a c o l1 6 2 ( 2 0 1 2 ) Early Hints of a Third Photoreceptor in the Mammalian RetinaThe perception of shapes, color and objects moving in the world begins in the outer retina where light is absorbed by photopigments that are integral membrane apoproteins (opsins) covalently linked to a retinaldehyde chromophore in the rod and cone photoreceptors. The capturing of photons by rod and cone photoreceptors initiates a signaling cascade in which photon capture is converted into an electrical signal. The simplest common pathway these signals take from the eye to the brain is from the photoreceptors to bipolar cells to ganglion cells. Retinal ganglion cells (RGCs) convey the signals centrally as action potentials, transmitted via their axons in the optic nerve, to higher brain regions for integration and the further processing required for conscious visual perception (Fig. 1). Among non-mammalian vertebrates, photoreceptors are also found in locations outside the retina, including the pineal gland and in the brain itself. These extra-ocular photoreceptors mediate tasks not associated directly with visual perception (non-image forming functions such as hormone regulation). However, since the pioneering descriptions of the vertebrate retina by Santiago Ramón y Cajal in the late 1800s, it was believed that t...

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“…A second study showed progressive loss in density, cell integrity and dendritic arborisation of ipRGCs in advanced stages of RP (Esquiva et al 2013) consistent with initial findings of ipRGC dysfunction in advanced AMD ). An example of this resistance to damage is shown in a study in patients with glaucoma that demonstrated the PIPR in patients with early glaucoma was similar to controls (Feigl et al 2011b), but lower in patients with advanced glaucoma (Feigl et al 2011b;Kankipati et al 2011). In patients with Leber's hereditary optic neuropathy (LHON), the sustained pupil response to blue light in the affected eye was similar to that in the healthy eye, suggesting a resistance to the intracellular metabolic disorder affecting the optic nerve caused by a genetic defect (Kawasaki et al 2010;Moura et al 2013).…”

Section: 6mentioning

confidence: 94%

“…IpRGCs have demonstrated enhanced survival after optic nerve injury and transection in rats (Li et al 2008;Perez de Sevilla Muller, Sargoy, Rodriguez & Brecha 2014) suggesting high injury resistance (Cui, Ren, Sollars, Pickard & So 2015), although studies in humans show ipRGC dysfunction in patients with glaucoma (Feigl, Mattes, Thomas & Zele 2011b;Gracitelli et al 2014;Kankipati, Girkin & Gamlin 2011) and more recently in glaucoma suspects (Adhikari et al 2016b). The initial evidence of altered ipRGC function in AMD is shown in a pilot study by , although little is known about the effect of AMD on ipRGC function in various stages of the disease.…”

Section: Intrinsically Photosensitive Retinal Ganglion Cell Functionmentioning

confidence: 99%

“…IpRGC function has been measured using the PIPR in diabetic patients without diabetic retinopathy (Feigl et al 2012b), glaucoma (Feigl et al 2011b;Gracitelli et al 2014;Kankipati et al 2011), retinitis pigmentosa Kawasaki, Crippa, Kardon, Leon & Hamel 2012;Markwell et al 2010), Leber's hereditary optic neuropathy (Kawasaki, Herbst, Sander & Milea 2010) and retinal dystrophy (Vugler, Semo, Joseph & Jeffery 2008). In AMD, the PLR has been used as a measure of outer retinal function (Asakawa, Ishikawa, Ichibe & Shimizu 2014;Brozou et al 2009;Nakayama, Nowak, Ishikawa, Asakawa & Ichibe 2014;Rosli et al 2012;Sabeti et al 2013;Sabeti et al 2011) and demonstrates a longer latency to constriction and reduction in maximum pupil constriction amplitude.…”

Section: 3mentioning

confidence: 99%

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