The Method of Silent Substitution for Examining Melanopsin Contributions to Pupil Control

Spitschan, Manuel; Woelders, Tom

doi:10.3389/fneur.2018.00941

Cited by 75 publications

(78 citation statements)

References 58 publications

(53 reference statements)

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“…The selectively altered function of various cone types, however, cannot be tested with standard photopic 3.0 ERGs. Due to the quite extensively overlapping spectral sensitivities of different photopigments [21], these tests reflect the summed activity of all three retinal cone types. Photopic 3.0…”

Section: Discussionmentioning

confidence: 99%

“…From the clinical point of view, our next investigative steps seem well defined: i) cone-specific ERGs using the "silent substitution" paradigm [43] to isolate individual (L, M, or S) cone responses [44] and thus support or exclude our selective cone dysfunction hypothesis; ii) post-illumination pupil response (PIPR) to test melanopsin expressing ipRGC function [21] and thus shed light on the extent of ipRGC damage. iii) long-term follow-up of POAG progression monitoring IOPs and visual field defects.…”

Section: Discussionmentioning

confidence: 99%

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Myopia-26, the female-limited form of early-onset high myopia is associated with retinal ganglion cell dysfunction and primary open angle glaucoma

Széll

Fehér

Maróti

et al. 2020

Preprint

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Background: Female-limited early-onset high myopia, also called Myopia-26 is a rare monogenic disorder characterized by severe short sightedness starting in early childhood and progressing to blindness potentially by the middle ages. Despite the X-linked locus of the mutated ARR3 gene, the disease paradoxically affects females only, with males being asymptomatic carriers. Previously, this disease has only been observed in Asian families and has not gone through detailed investigation concerning collateral symptoms or pathogenesis Results: We found a large Hungarian family displaying female-limited early-onset high myopia. Whole exome sequencing of two individuals identified a novel nonsense mutation (c.214C>T, p.Arg72*) in the ARR3 gene. We carried out basic ophthalmological testing for 18 family members, as well as detailed ophthalmological examination (intraocular pressure, axial length, fundus appearance, optical coherence tomography, visual field- and colour vision testing) and electrophysiology tests (standard and multifocal electroretinography, pattern electroretinography and visual evoked potentials) for eight individuals. We found variously impaired visual fields in four affected myopic females and a carrier male. Abnormal pattern electroretinography responses were detected in both symptomatic and carrier patients. Conclusions: This is the first description of a Caucasian family displaying Myopia-26. Pattern electroretinography implies retinal ganglion cell dysfunction present in both sexes. In conjunction with the visual field loss, this suggests the development of age-related open angle glaucoma in addition to high myopia, both attributable to the rare genetic variant of ARR3. We present two hypotheses that could potentially explain the pathomechanism of this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Myopia-26, the female-limited form of early-onset high myopia is associated with retinal ganglion cell dysfunction and primary open angle glaucoma

Széll

Fehér

Maróti

et al. 2020

Preprint

View full text Add to dashboard Cite

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“…Metamers are designed to have balanced changes in the intensity of various wavelengths of light in order to stimulate a particular photoreceptor, but without altering the effective photon flux for other classes of photoreceptors. This method has been used successfully to investigate melanopsin involvement in visual processing in mice [81][82][83][84][85] and the photoreceptor contributions to the pupillary light reflex in humans [86][87][88][89]. Allen and colleagues built a visual display capable of presenting metameric images differing in melanopsin effective irradiance to humans.…”

Section: Discussionmentioning

confidence: 99%

How Does Light Regulate Mood and Behavioral State?

Milosavljevic

2019

Clocks & Sleep

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The idea that light affects mood and behavioral state is not new. However, not much is known about the particular mechanisms and circuits involved. To fully understand these, we need to know what properties of light are important for mediating changes in mood as well as what photoreceptors and pathways are responsible. Increasing evidence from both human and animal studies imply that a specialized class of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), plays an important role in the light-regulated effects on mood and behavioral state, which is in line with their well-established roles in other non-visual responses (pupillary light reflex and circadian photoentrainment). This paper reviews our current understanding on the mechanisms and paths by which the light information modulates behavioral state and mood.

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“…We generated our S-cone-selective stimuli using the method of silent substitution [6, 7]. In the method of silent substitution, pairs of spectra are generated as mixtures of the ten primaries lights which produce a difference in only one photoreceptor class (in this case, the stimulated S cones), while there is no difference in the other photoreceptors (in this case, the silenced L and M cones, rods, and melanopsin).…”

Section: Online Supplement: Materials and Methodsmentioning

confidence: 99%

No evidence for an S cone contribution to the human circadian response to light

Spitschan

Lazar

Yetik

et al. 2019

Preprint

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Exposure to even moderately bright, short-wavelength light in the evening can strongly suppress the production of melatonin and can delay our circadian rhythm. These effects are mediated by the retinohypothalamic pathway, connecting a subset of retinal ganglion cells to the circadian pacemaker in the suprachiasmatic nucleus (SCN) in the brain. These retinal ganglion cells directly express the photosensitive protein melanopsin, rendering them intrinsically photosensitive (ipRGCs). But ipRGCs also receive input from the classical photoreceptors — the cones and rods. Here, we examined whether the short-wavelength-sensitive (S) cones contribute to circadian photoreception by using lights which differed exclusively in the amount of S cone excitation by almost two orders of magnitude (ratio 1:83), but not in the excitation of long-wavelength-sensitive (L) and medium-wavelength-sensitive (M) cones, rods, and melanopsin. We find no evidence for a role of S cones in the acute alerting and melatonin supressing response to evening light exposure, pointing to an exclusive role of melanopsin in driving circadian responses.

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The Method of Silent Substitution for Examining Melanopsin Contributions to Pupil Control

Cited by 75 publications

References 58 publications

Myopia-26, the female-limited form of early-onset high myopia is associated with retinal ganglion cell dysfunction and primary open angle glaucoma

Myopia-26, the female-limited form of early-onset high myopia is associated with retinal ganglion cell dysfunction and primary open angle glaucoma

How Does Light Regulate Mood and Behavioral State?

No evidence for an S cone contribution to the human circadian response to light

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