Electrophysiological responses from intrinsically photosensitive retinal ganglion cells are diminished in glaucoma patients

Kuze, Manami; Morita, Takeshi; Fukuda, Yumi; Kondo, Mineo; Ohta, Michio; Ayaki, Masahiko

doi:10.1016/j.optom.2016.07.004

Cited by 18 publications

(27 citation statements)

References 40 publications

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“…22,24 In this study, the reduction in pupillary constriction amplitudes to moderate and high irradiances of blue light (above 11.0 Log photons/cm 2 /s) corresponding to the range of activation of ipRGCs 12 is indicative of altered intrinsic photosensitivity or a degeneration of these cells in earlystage POAG. Our findings are in agreement with recent studies showing altered electrophysiologic responses of ipRGCs in patients with glaucoma 17 and with earlier reports in rodent models of chronic ocular hypertension showing a reduction of ipRGCs and their brain projections. 15,33 Recent histologic findings in glaucomatous human retinas have suggested significant loss of ipRGCs in the severe stages of the disease, but earlier alterations were not clearly documented in this article.…”

Section: Discussionsupporting

confidence: 94%

“…14 The discovery of these inner retina photoreceptors offers a potential way for glaucoma screening with animal and human histological and electrophysiological studies asserting a loss or disruption of ipRGCs in this disease. [15][16][17] Pupillometry is a simple, noninvasive, and objective procedure that consists of measuring pupil size and reactivity. Pupillary light responses are dependent on the integrity of ipRGC projections and the interplay between the outer (red/ green-shifted peak sensitivity) and inner (blue-shifted peak sensitivity) retinal photoreception.…”

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confidence: 99%

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Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma

et al. 2018

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Section: Discussionsupporting

confidence: 94%

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confidence: 99%

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma

et al. 2018

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“…1.2 million, only 9.6-36 thousand RGCs contain melanopsin and are intrinsically photosensitive. [3][4][5] In a healthy retina, a light impulse -after being transduced into a biochemical impulse -is transmitted via the cortical and nonimage-forming pathways towards the appropriate centers in the brain. However, in the glaucomatous retina, the same light impulse causes less pronounced cortical and nonimage-forming input towards the brain due to the presence of fewer RGCs in the retina (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…In that study, glaucomatous patients showed diminished responses of the ipRGCs in ERG. 4 The reduced blue-red post-illumination pupil response indicates a characteristic impairment of the melanopsin-driven pathway of ipRGCs in patients with glaucoma. Other studies have shown that reduced maximal relative amplitude and increased slope of the response during exposure to the 4-second red stimulus suggest a disturbed synaptic function and an altered interaction between outer photoreceptors, RGCs and ipRGCs.…”

Section: Introductionmentioning

confidence: 99%

Pupil autoregulation impairment as an early marker of glaucomatous damage

Szmigiel¹,

Przeździecka-Dołyk²,

Olszewski³

et al. 2019

Adv Clin Exp Med

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Background. Glaucoma, a degenerative and progressive disease, leads to structural and functional changes in the optic nerve head and retinal ganglion cells (RGCs), while the vasculature of the iris stays intact. Objectives. The aim of this study was to determine whether the coherence level associated with pupil geometry and peripheral arterial pulsation can be the basis for differentiating glaucoma and glaucomasuspected patients from a control group. Material and methods. This is an investigator-initiated, single-center prospective cohort study. Patients with diagnosed glaucoma (glaucoma group-GG) or glaucoma suspects (glaucoma suspects group-GSG), as well as healthy participants (control group-CG), were prospectively enrolled in the study. Glaucomadiagnosed patients and glaucoma suspects who converted to glaucoma within 5 years were included. All patients underwent a full ophthalmological examination that included measurements of the thicknesses of the retinal nerve fiber layer (RNFL) and the ganglion cell complex (GCC) along with other parameters. A custom-made pupilometer was synchronized with a pulsometer to simultaneously record an image of the pupil and the peripheral arterial pulsation signal. All readings were processed with a script developed by the researchers. The main indicator of an increased influence of the vascular structures of the iris on pupil geometry in the patients and CG were the coherence levels (levC) between parameters describing the pupillary shape and peripheral arterial pulsation. Results. Differences in the median value of the levCpS, levCpε and levCpθ parameters between the GG and GSG compared to the CG were found (p < 0.001). During the follow-up period, a larger decrease was observed in RNFL thickness and GCC thickness in the GSG than in the GG (p < 0.05). Strong correlations were found between levCpS and RNFL and GCC loss among the GSG group (p < 0.001), while in the GG this parameter correlated with RNFL and GCC thickness (p < 0.001). Conclusions. This is the first attempt to relate changes in the neuronal signaling pathways in glaucoma to the vascular-dependent changes of pupil geometry. The findings presented herein suggest that this approach can be used to determine which glaucoma suspects have autonomic system impairment in the eye, increasing their probability of glaucoma conversion.

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“…A typical ERG response consists of a, b, c, d waves and oscillatory potentials origination from rodcone, ON bipolar and muller cells, pigment epithelium, OFF bipolar cells and amacrine cells respectively (Hamel, 2007;Marmor & Hock, 1982;Wachtmeister et al, 1978). A recent study optimized stimuli to match the ipRGC spectral sensitivity and showed that ERG response can be elicited from ipRGCs (Kuze, Morita, Fukuda, Kondo, Tsubota, & Ayaki, 2016).…”

Section: Retinal Function In Depressive Disordersmentioning

confidence: 99%

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

Ojha¹

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Aberrant light exposure causes depression in animals through a pathway involving the recently discovered intrinsically photosensitive Retinal Ganglion Cells (ipRGCs). The photopigment melanopsin expressed in ipRGCs encodes irradiance to signal to the nonimage-forming centres of the brain, including the suprachiasmatic nucleus (SCN) for circadian photoentrainment and the olivary pretectal nucleus (OPN) to control the pupil light reflex. Mouse models have further identified ipRGC projections to the brain nuclei that regulate mood and behaviour. In humans, the post-illumination pupil response (PIPR), a sustained pupillary constriction after light offset, is used as a direct and non-invasive biomarker of ipRGC function.The PIPR amplitude is reduced in humans with seasonal affective disorder (SAD) that shows a seasonal variation in depressive episodes with a peak manifestation in winter when the solar light exposure is low, but a recent study including patients with non-seasonal depressive disorder did not detect ipRGC dysfunction. Moreover, neither study measured the ambient light exposure levels in patients with depression for comparison to healthy individuals without depression. The knowledge of the role of light coding cells (ipRGCs) in major depressive disorder (MDD) is incomplete unless the relationship between ambient light exposure levels and melanopsin function is evaluated. This study aims to measure the environmental light exposure levels and their relationship with melanopsin-mediated PIPR in non-seasonal depression. It is hypothesised that the patients with non-seasonal depression are exposed to low light levels and this is associated with impaired melanopsin function.A sample of 22 adults was recruited, including people with non-seasonal depression (n = 8, median age: 35 years) and healthy age-matched controls (n = 14, median age: 29 years).The presence of a DSM-IV MDD was assessed using the Mini International Neuropsychiatry ii Interview (MINI 6). The severity of depression symptoms was assessed with the Beck Depression Inventory (BDI-II). Individuals with recurrent MDD assessed with the MINI and a positive screen on the Seasonal Pattern Assessment Questionnaire and the Hamilton Depression Rating Scale-SAD (HDRS-SAD) were excluded as SAD. Both groups had visual acuity ≥ 6/6, normal colour vision and intraocular pressure (IOP) ≤ 21 mmHg, no corneal and lenticular opacities and normal retinae and optic discs. The ipRGC-mediated PIPR was measured using a short duration (1 s) high irradiance (15.5 log quanta.cm -2 .s -1 ) short wavelength (blue appearing) light stimulus with a custom built Maxwellian view pupillometer. Light exposure levels, sleep-wake times and sleep efficiency were determined over 2 weeks with an ambulatory light sensor device (Geneactive).The mean daily light exposure levels were similar between the groups and there were no statistically significant differences between the groups for light exposure levels as a function of clock hours, nor in the total number of minutes of exposu...

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Electrophysiological responses from intrinsically photosensitive retinal ganglion cells are diminished in glaucoma patients

Cited by 18 publications

References 40 publications

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma

Pupillary Responses to Full-Field Chromatic Stimuli Are Reduced in Patients with Early-Stage Primary Open-Angle Glaucoma

Pupil autoregulation impairment as an early marker of glaucomatous damage

An Evaluation of Melanopsin Function and Light Exposure in Depressive Disorders

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