Journal article
Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics: A Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis
JAMA neurology, Vol.74(5), pp.574-582
05/01/2017
DOI: 10.1001/jamaneurol.2016.5131
PMCID: PMC5822208
PMID: 28135360
Abstract
A neurophysiologic signature of the melanopsin-mediated persistent constriction phase of the pupillary light reflex may represent a surrogate biomarker for the integrity of the retinohypothalamic tract, with potential utility for investigating alterations in homeostatic mechanisms associated with brain disorders and implications for identifying new treatments. To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. The case-control study was an experimental assessment of various stimulus-induced pupillary response characteristics and was conducted at a university clinical center for MS from September 6, 2012, to February 2015. Twenty-four patients with MS (48 eyes) and 15 individuals serving as controls (30 eyes) participated. The melanopsin-mediated, sustained pupillary constriction phase response following cessation of a blue light stimulus was compared with the photoreceptor-mediated pupillary constriction phase response following cessation of a red light stimulus. Optical coherence tomography was used to characterize the association between pupillary response characteristics and alterations in retinal architecture, specifically, the thickness of the retinal ganglion cell layer and inner plexiform layer (GCL + IPL). Association of pupillary response characteristics with alterations in retinal architecture. Of 24 patients with MS included in the analysis, 17 were women (71%); mean (SD) age was 47 (11) years. Compared with eyes from individuals with MS who had normal optical coherence tomography-derived measures of retinal GCL + IPL thickness, eyes of patients who had GCL + IPL thickness reductions to less than the first percentile exhibited a correspondingly significant attenuation of the melanopsin-mediated sustained pupillary response (mean [SD] pupillary diameter ratios at a point in time, 0.18 [0.1] vs 0.33 [0.09]; P < .001, generalized estimating equation models accounting for age and within-patient intereye correlations). In this case-control study, attenuation of the melanopsin-mediated sustained pupillary constriction response was significantly associated with thinning of the GCL + IPL sector of the retina in the eyes of patients with MS, particularly those with a history of acute optic neuritis. Melanopsin-containing ganglion cells in the retina represent, at least in part, the composition of the retinohypothalamic tract. As such, our findings may signify the ability to elucidate a putative surrogate neurophysiologic signature that correlates with a constellation of homeostatic mechanisms in both health and illness.
Details
- Title: Subtitle
- Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics: A Putative Pathophysiologic Signature for the Retino-Hypothalamic Tract in Multiple Sclerosis
- Creators
- Ethan Meltzer - The University of Texas Southwestern Medical CenterPeter V Sguigna - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasAdnan Subei - Department of Neurology, Michigan State University, East LansingShin Beh - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasEric Kildebeck - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas3Center for Engineering Innovation, University of Texas at DallasDarrel Conger - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasAmy Conger - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasMarlen Lucero - Student, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasBenjamin S Frohman - Student, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasAshley N Frohman - Student, Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasShiv Saidha - Department of Neurology, Johns Hopkins Hospital, Baltimore, MarylandSteven Galetta - Department of Neurology, Population Health, New York University School of Medicine, New YorkPeter A Calabresi - Department of Neurology, Johns Hopkins Hospital, Baltimore, MarylandRobert Rennaker - Department of Bioengineering, University of Texas at DallasTeresa C Frohman - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at DallasRandy H Kardon - Department of Ophthalmology, University of Iowa, Iowa City9Iowa City Veterans Affairs Center for Prevention and Treatment of Visual Loss, Iowa CityLaura J Balcer - Department of Neurology, Population Health, New York University School of Medicine, New York10Department of Ophthalmology, New York University School of Medicine, New YorkElliot M Frohman - Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center at Dallas7Department of Bioengineering, University of Texas at Dallas11Department of Ophthalmology, University of Texas Southwestern Medical Center at Dallas
- Resource Type
- Journal article
- Publication Details
- JAMA neurology, Vol.74(5), pp.574-582
- DOI
- 10.1001/jamaneurol.2016.5131
- PMID
- 28135360
- PMCID
- PMC5822208
- NLM abbreviation
- JAMA Neurol
- ISSN
- 2168-6149
- eISSN
- 2168-6157
- Publisher
- United States
- Language
- English
- Date published
- 05/01/2017
- Academic Unit
- Iowa Neuroscience Institute; Ophthalmology and Visual Sciences
- Record Identifier
- 9983980057002771
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