Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma

Gracitelli, Carolina P. B.; Duque-Chica, Gloria L.; Roizenblatt, Marina; Moura, Ana Laura de Araújo; Nagy, Balázs Vince; Melo, Geraldine Ragot de; Borba, Paula; Teixeira, Sérgio Henrique; Tufik, Sérgio; Ventura, Dora Fix; Paranhos, Augusto

doi:10.1016/j.ophtha.2015.02.030

Cited by 80 publications

(102 citation statements)

References 50 publications

(53 reference statements)

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“…Our hypothesis was that altered ipRGC function in AMD will lead to sleep and mood disturbances due to their projections to corresponding brain areas. Based on previous studies (Gracitelli et al 2015;LeGates et al 2012), we proposed that aberrant light signalling through dysfunctional ipRGCs will contribute to these behavioural changes. A positive correlation was observed between reduced ipRGC function as measured by the melanopsin mediated post-illumination pupil response (PIPR) and poorer sleep efficiency, with ipRGC dysfunction accounting for 13% of the reduced sleep efficiency.…”

Section: 6mentioning

confidence: 91%

“…Two recent studies observed that sleep duration was altered in advanced AMD patients; sleep duration decreased in wet AMD and increased in dry AMD (Khurana et al 2016;Pérez-Canales et al 2016) but the effect of aberrant ipRGC signalling in AMD Maynard et al 2015) as a contributing factor was not evaluated. Supporting evidence for an association between ipRGC dysfunction and sleep disorders is provided in primary open angle glaucoma patients (Feigl et al 2011b;Kankipati et al 2011) where there is also decreased sleep quality (Gracitelli et al 2016;Gracitelli et al 2015).…”

Section: 3mentioning

confidence: 99%

“…Studies in melanopsin knock-out mice show sleep disturbances where they sleep for approximately one hour less than wild-type mice (Tsai et al 2009) while human studies show that ipRGC deficits are associated with sleep disorders in glaucoma (Gracitelli et al 2015) and their function is reduced in seasonal affective disorder (Roecklein et al 2013). With the high prevalence of depression in AMD (Brody et al 2001;Casten & Rovner 2013) and altered sleep duration that is dependent on AMD type (wet or dry) (Khurana et al 2016;Pérez-Canales, Rico-Sergado & Pérez-Santonja 2016), ipRGC dysfunction in AMD may contribute to these disorders.…”

Section: Statement Of Original Authorshipmentioning

confidence: 99%

“…There is a high frequency of sleep disturbances in people with vision loss who retain light perception, becoming more severe and more common in people with total vision loss and no light perception (Tabandeh et al 1998). Sleep disorders have been linked to glaucoma (Agorastos et al 2013;Ayaki, Shiba, Negishi & Tsubota 2016;Jean-Louis, Zizi, Lazzaro & Wolintz 2008;Wang, Zhang, Ding & Wang 2013) which has further been associated with ipRGC dysfunction (Gracitelli et al 2016;Gracitelli et al 2014;Gracitelli et al 2015). Altered sleep duration has been demonstrated in AMD patients (Khurana et al 2016;Pérez-Canales et al 2016) although no link has been established with ipRGC function.…”

Section: Iprgc Function and Sleep In Advanced Amd 24mentioning

confidence: 99%

“…IpRGCs also signal to the olivary pretectal nucleus (OPN) for mediation of the pupil light reflex (PLR) (Gamlin et al 2007;Kawasaki & Kardon 2007) and in particular the post-illumination pupil response (PIPR) (Adhikari et al 2016a;Gamlin et al 2007;Kawasaki & Kardon 2007;Markwell et al 2010), which is an emerging method for the direct assessment of ipRGC function in healthy and diseased eyes and in persons with chronobiological disorders Feigl et al 2012b;Gamlin et al 2007;Gracitelli et al 2016;Gracitelli et al 2014;Gracitelli et al 2015;Kawasaki & Kardon 2007;Markwell et al 2010;Maynard et al 2015). Two recent studies observed that sleep duration was altered in advanced AMD patients; sleep duration decreased in wet AMD and increased in dry AMD (Khurana et al 2016;Pérez-Canales et al 2016) but the effect of aberrant ipRGC signalling in AMD Maynard et al 2015) as a contributing factor was not evaluated.…”

Section: 3mentioning

confidence: 99%

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Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

Maynard¹

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Section: 6mentioning

confidence: 91%

Section: 3mentioning

confidence: 99%

Section: Statement Of Original Authorshipmentioning

confidence: 99%

Section: Iprgc Function and Sleep In Advanced Amd 24mentioning

confidence: 99%

Section: 3mentioning

confidence: 99%

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Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

Maynard¹

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Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics

et al. 2017

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IMPORTANCE 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.OBJECTIVE To characterize abnormalities of retinal architecture in patients with multiple sclerosis (MS) and corresponding alterations in the melanopsin-mediated sustained pupillary constriction response. DESIGN, SETTING, AND PARTICIPANTSThe 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). MAIN OUTCOMES AND MEASURESAssociation of pupillary response characteristics with alterations in retinal architecture. RESULTSOf 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). CONCLUSIONS AND RELEVANCEIn 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.

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Differential effects of experimental glaucoma on intrinsically photosensitive retinal ganglion cells in mice

Gao

Griner

Liu

et al. 2022

J of Comparative Neurology

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Glaucoma is a group of eye diseases characterized by retinal ganglion cell (RGC) loss and optic nerve damage. Studies, including this study, support that RGCs degenerate and die in a type‐specific manner following the disease insult. Here we specifically examined one RGC type, the intrinsically photosensitive retinal ganglion cell (ipRGC), and its associated functional deficits in a mouse model of experimental glaucoma. We induced chronic ocular hypertension (OHT) by laser photocoagulation and then characterized the survival of ipRGC subtypes. We found that ipRGCs suffer significant loss, similar to the general RGC population, but ipRGC subtypes are differentially affected following chronic OHT. M4 ipRGCs, which are involved in pattern vision, are susceptible to chronic OHT. Correspondingly, mice with chronic OHT experience reduced contrast sensitivity and visual acuity. By comparison, M1 ipRGCs, which project to the suprachiasmatic nuclei to regulate circadian rhythmicity, exhibit almost no cell loss following chronic OHT. Accordingly, we observed that circadian re‐entrainment and circadian rhythmicity are largely not disrupted in OHT mice. Our study demonstrates the link between subtype‐specific ipRGC survival and behavioral deficits in glaucomatous mice. These findings provide insight into glaucoma‐induced visual behavioral deficits and their underlying mechanisms.

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Intrinsically Photosensitive Retinal Ganglion Cell Activity Is Associated with Decreased Sleep Quality in Patients with Glaucoma

Cited by 80 publications

References 50 publications

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

Image and Non-Image Forming Melanopsin Function in Age-Related Macular Degeneration

Retinal Architecture and Melanopsin-Mediated Pupillary Response Characteristics

Differential effects of experimental glaucoma on intrinsically photosensitive retinal ganglion cells in mice

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