Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

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

doi:10.1155/2016/5317371

Cited by 23 publications

(23 citation statements)

References 48 publications

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“…10,11 There is evidence that photoreceptor dysfunction, in particular, the impairment of melanopsin containing intrinsically photosensitive retinal ganglion cells (ipRGCs) can contribute to sleep disturbances in eye diseases such as glaucoma and AMD. [12][13][14][15] However, such relationship between ipRGC function and sleep has not been investigated in patients with diabetes, although there is evidence for reduced melanopsin function 16 and anatomical loss of ipRGCs in advanced DR. 17 In early stages of diabetes, retinal neurodegeneration occurs before the clinical manifestation of retinopathy. 18 At preretinopathy stage, anatomic alterations in the outer and inner retina can be detected, 19,20 and it has been proposed that rod photoreceptors are more vulnerable due to their higher oxygen demand than cones.…”

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confidence: 99%

Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes

Dumpala

Zele

Feigl

2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Light transmitted by retinal photoreceptors provides the input for circadian photoentrainment. In diabetes, there is a high prevalence of circadian and sleep disruption but the underlying causes are not well understood. Patients with diabetes can exhibit dysfunctional photoreceptors but their role in circadian health is not known. Here we quantify photoreceptor function and contributions to circadian health and sleep in patients with diabetes without diabetic retinopathy and healthy controls. METHODS. Rod, cone, and melanopsin function was derived using chromatic pupillometry in 47 participants including 23 patients with type 2 diabetes and 24 age-matched healthy controls after an ophthalmic examination including retinal thickness assessment using optical coherence tomography. Circadian health was determined using dim light melatonin onset (DLMO) and sleep questionnaires; light exposure was measured using actigraphy. RESULTS. Compared with the control group, the patients with diabetes had a significantly earlier DLMO (1 hour) (P ¼ 0.008), higher subjective sleep scores (P < 0.05), a reduction in pupil constriction amplitude for red stimuli (P ¼ 0.039) and for the early postillumination pupil response (PIPR) for blue (P ¼ 0.024) stimuli. There were no between-group differences in the light exposure pattern, activity levels, and intrinsic melanopsin-mediated PIPR amplitude (P > 0.05). A significant correlation was evident between outer retinal thickness and DLMO (r ¼ À0.65, P ¼ 0.03) and the pupil constriction amplitude (r ¼ 0.63, P ¼ 0.03); patients with thinner retina had earlier DLMO and lower pupil amplitudes. CONCLUSIONS. We infer that the observed changes in circadian function in patients with no diabetic retinopathy are due to structural and functional outer retinal rod photoreceptor deficits at early stage of diabetic eye disease.

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confidence: 99%

Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes

Dumpala

Zele

Feigl

2019

Invest. Ophthalmol. Vis. Sci.

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“…However, in other rodent models mRGCs are reported to be vulnerable to IOP damage to the same extent as conventional RGCs (Drouyer et al, 2008;de Zavalía et al, 2011) and recently, in experimental rat and mouse glaucoma models, a 50% loss of mRGCs was described . Similarly, human functional studies investigating PLR and light-induced nocturnal melatonin suppression in glaucoma patients have reported reduced responses in patients compared to controls suggesting a vulnerability of mRGCs in glaucoma (Gracitelli et al, 2016(Gracitelli et al, , 2015(Gracitelli et al, , 2014Kelbsch et al, 2016;Pérez-Rico et al, 2010;Nissen et al, 2014;Rukmini et al, 2015). However, in a severely affected glaucoma patient Zhou and colleagues showed persistence of the PLR implicating the survival of mRGCs despite the severe optic neuropathy (Zhou et al, 2014).…”

Section: Glaucomamentioning

confidence: 97%

Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but not always

et al. 2017

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Melanopsin retinal ganglion cells (mRGCs) are intrinsically photosensitive RGCs deputed to non-image forming functions of the eye such as synchronization of circadian rhythms to light-dark cycle. These cells are characterized by unique electrophysiological, anatomical and biochemical properties and are usually more resistant than conventional RGCs to different insults, such as axotomy and different paradigms of stress. We also demonstrated that these cells are relatively spared compared to conventional RGCs in mitochondrial optic neuropathies (Leber's hereditary optic neuropathy and Dominant Optic Atrophy). However, these cells are affected in other neurodegenerative conditions, such as glaucoma and Alzheimer's disease. We here review the current evidences that may underlie this dichotomy. We also present our unpublished data on cell experiments demonstrating that melanopsin itself does not explain the robustness of these cells and some preliminary data on immunohistochemical assessment of mitochondria in mRGCs.

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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%

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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Relationship between Daytime Sleepiness and Intrinsically Photosensitive Retinal Ganglion Cells in Glaucomatous Disease

Cited by 23 publications

References 48 publications

Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes

Outer Retinal Structure and Function Deficits Contribute to Circadian Disruption in Patients With Type 2 Diabetes

Melanopsin-expressing retinal ganglion cells are resistant to cell injury, but not always

Pupil autoregulation impairment as an early marker of glaucomatous damage

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