Melanopsin-mediated pupil function is impaired in Parkinson’s disease

Joyce, Daniel S.; Feigl, Beatrix; Kerr, Graham; Roeder, Luisa; Zele, Andrew J.

doi:10.1038/s41598-018-26078-0

“…In the last years the mRGC-mediated pupil light response has been investigated in various neurological disorders, including IIH, MS, and PD (31–34).…”

Section: Melanopsin Rgcs and Pupil In Other Neurological Disordersmentioning

confidence: 99%

“…The PLR mediated by mRGCs has been investigated in different ophthalmological conditions including glaucoma (16–18), retinitis pigmentosa (19), diabetes (20), Leber's congenital amaurosis (14), age-related macular degeneration (21), and ischemic optic neuropathies (22, 23). Moreover, various neurological and psychiatric disorders have been evaluated, including hereditary optic neuropathies (24–29), seasonal affective disorder (SAD) (30), idiopathic intracranial hypertension (IIH) (31, 32), multiple sclerosis (MS) (33), and Parkinson's disease (PD) (34).…”

Section: Introductionmentioning

confidence: 99%

Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology

Morgia

¹

,

Carelli

²

,

Carbonelli

³

2018

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Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs that mediate many relevant non-image forming functions of the eye, including the pupillary light reflex, through the projections to the olivary pretectal nucleus. In particular, the post-illumination pupil response (PIPR), as evaluated by chromatic pupillometry, can be used as a reliable marker of mRGC function in vivo. In the last years, pupillometry has become a promising tool to assess mRGC dysfunction in various neurological and neuro-ophthalmological conditions. In this review we will present the most relevant findings of pupillometric studies in glaucoma, hereditary optic neuropathies, ischemic optic neuropathies, idiopathic intracranial hypertension, multiple sclerosis, Parkinson's disease, and mood disorders. The use of PIPR as a marker for mRGC function is also proposed for other neurodegenerative disorders in which circadian dysfunction is documented.

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“…PIPR measurements have been made in numerous clinical conditions, including multiple sclerosis, Parkinson's disease, idiopathic intracranial hypertension, traumatic brain injury, glaucoma, diabetes, retinitis pigmentosa, Leber's hereditary optic neuropathy, Smith-Magenis syndrome, and depression. 21 – 32 …”

mentioning

confidence: 99%

Pulses of Melanopsin-Directed Contrast Produce Highly Reproducible Pupil Responses That Are Insensitive to a Change in Background Radiance

McAdams

¹

,

Igdalova

²

,

Spitschan

³

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrally narrowband stimuli.MethodsThree-second unipolar pulses were used to elicit pupil responses in human subjects across three sessions. Thirty subjects were studied in session 1, and most returned for sessions 2 and 3. The stimuli of primary interest were “silent substitution” cone- and melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, whereas session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape.ResultsGroup average pupil responses for all stimuli overlapped extensively across sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone- and melanopsin-directed pupil responses from session 3 were highly similar to those from sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light.ConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups.

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“…Particular attention is paid to the behavior of the pupil at relatively delayed time periods, including after stimulus offset (i.e., 'post-illumination'), when melanopsin is found to exert greater influence over pupil size relative to the cones 11,20 . PIPR measurements have been made in numerous clinical conditions, including multiple sclerosis, Parkinson's disease, idiopathic intracranial hypertension, traumatic brain injury, glaucoma, diabetes, retinitis pigmentosa, Leber's hereditary optic neuropathy, Smith-Magenis syndrome, and depression [21][22][23][24][25][26][27][28][29][30][31][32] .…”

Section: Introductionmentioning

confidence: 99%

Pulses of melanopsin-directed contrast produce highly reproducible pupilresponses that are insensitive to a change in background radiance

McAdams

¹

,

Igdaolva

²

,

Spitschan

³

et al. 2018

Preprint

0

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PurposeTo measure the pupil response to pulses of melanopsin-directed contrast, and compare this response to those evoked by cone-directed contrast and spectrallynarrowband stimuli.Methods 3-second unipolar pulses were used to elicit pupil responses in human subjects across 3 sessions. Thirty subjects were studied in Session 1, and most returned for Sessions 2 and 3. The stimuli of primary interest were "silent substitution" coneand melanopsin-directed modulations. Red and blue narrowband pulses delivered using the post-illumination pupil response (PIPR) paradigm were also studied. Sessions 1 and 2 were identical, while Session 3 involved modulations around higher radiance backgrounds. The pupil responses were fit by a model whose parameters described response amplitude and temporal shape. ResultsGroup average pupil responses for all stimuli overlapped extensively across Sessions 1 and 2, indicating high reproducibility. Model fits indicate that the response to melanopsin-directed contrast is prolonged relative to that elicited by cone-directed contrast. The group average cone-and melanopsin-directed pupil responses from Session 3 were highly similar to those from Sessions 1 and 2, suggesting that these responses are insensitive to background radiance over the range studied. The increase in radiance enhanced persistent pupil constriction to blue light. ConclusionsThe group average pupil response to stimuli designed through silent substitution provides a reliable probe of the function of a melanopsin-mediated system in humans. As disruption of the melanopsin system may relate to clinical pathology, the reproducibility of response suggests that silent substitution pupillometry can test if melanopsin signals differ between clinical groups. Methods SubjectsSubjects were recruited from the community of students and staff at the University of Pennsylvania. Exclusion criteria for enrollment included a prior history of glaucoma or a negative reaction to pupil-dilating eye drops. During an initial screening session, subjects were also excluded for abnormal color vision as determined by the Ishihara plates 43 or visual acuity below 20/40 in each eye as determined using a distance Snellen eye chart. Subjects completed a brief, screening pupillometry session. We excluded at this preliminary stage subjects who were unable to provide high-quality pupil tracking data (details below). Poor data quality was found to result from difficulty suppressing blinks or from poor infra-red contrast between the pupil and iris.A total of 32 subjects were recruited and completed initial screening. Two of these subjects were excluded after screening due to poor data quality (e.g., excessive loss of data points from blinking) as determined by pre-registered criteria. Thirty subjects thus successfully completed Session 1 and provided data for analysis. These subjects were between 19-33 years of age (mean 25.93 ± 4.24 SD). Fourteen subjects identified as male, 15 female, and one declined to provide a gender identification. Of this group of 30 sub...

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Melanopsin-mediated pupil function is impaired in Parkinson’s disease

Cited by 65 publications

References 83 publications

Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology

Melanopsin Retinal Ganglion Cells and Pupil: Clinical Implications for Neuro-Ophthalmology

Pulses of Melanopsin-Directed Contrast Produce Highly Reproducible Pupil Responses That Are Insensitive to a Change in Background Radiance

Pulses of melanopsin-directed contrast produce highly reproducible pupilresponses that are insensitive to a change in background radiance

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