scholarly journals Nicotinamide-Rich Diet in DBA/2J Mice Preserves Retinal Ganglion Cell Metabolic Function as Assessed by PERG Adaptation to Flicker

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1910 ◽  
Author(s):  
Tsung-Han Chou ◽  
Giovanni Luca Romano ◽  
Rosario Amato ◽  
Vittorio Porciatti
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Pattern Electroretinogram ◽  
Retinal Ganglion ◽  
Metabolic Demand ◽  
Vitamin B3 ◽  
Non Invasive ◽  
Soma Size ◽  
Baseline Test ◽  
Optic Nerve Disorders

Flickering light increases metabolic demand in the inner retina. Flicker may exacerbate defective mitochondrial function in glaucoma, which will be reflected in the pattern electroretinogram (PERG), a sensitive test of retinal ganglion cell (RGC) function. We tested whether flicker altered the PERG of DBA/2J (D2) glaucomatous mice and whether vitamin B3-rich diet contributed to the flicker effect. D2 mice fed with either standard chow (control, n = 10) or chow/water enriched with nicotinamide (NAM, 2000 mg/kg per day) (treated, n = 10) were monitored from 3 to 12 months. The PERG was recorded with superimposed flicker (F-PERG) at either 101 Hz (baseline) or 11 Hz (test), and baseline-test amplitude difference (adaptation) evaluated. At endpoint, flat-mounted retinas were immunostained (RBPMS and mito-tracker). F-PERG adaptation was 41% in 3-month-old D2 and decreased with age more in control D2 than in NAM-fed D2 (GEE, p < 0.01). At the endpoint, F-PERG adaptation was 0% in control D2 and 17.5% in NAM-fed D2, together with higher RGC density (2.4×), larger RGC soma size (2×), and greater intensity of mitochondrial staining (3.75×). F-PERG adaptation may provide a non-invasive tool to assess RGC autoregulation in response to increased metabolic demand and test the effect of dietary/pharmacological treatments on optic nerve disorders.

scholarly journals Modeling Retinal Ganglion Cell Dysfunction in Optic Neuropathies

2021 ◽  
Author(s):  
Vittorio Porciatti ◽  
Tsung-Han Chou
Keyword(s):  
Cell Death ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Pattern Electroretinogram ◽  
Retinal Ganglion ◽  
Response Dynamics ◽  
Cell Dysfunction ◽  
Non Invasive ◽  
Neuroprotective Strategies ◽  
Cellular Dysfunction

As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, sensitive assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. Here we offer a conceptual framework to identify progressive stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies based on non-invasive pattern electroretinogram (PERG), to differentiate phenotypic and altered RGC response dynamics, to assess susceptibility to stressors and to assess reversible dysfunction.

scholarly journals Adaptation of retinal ganglion cell function during flickering light in the mouse

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Tsung-Han Chou ◽  
Jonathon Toft-Nielsen ◽  
Vittorio Porciatti
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Cell Function ◽  
Temporal Dynamics ◽  
Pattern Electroretinogram ◽  
Mouse Strains ◽  
Retinal Ganglion ◽  
Response Dynamics ◽  
Flickering Light ◽  
Induced Changes

AbstractRapid dilation of retinal vessels in response to flickering light (functional hyperemia) is a well-known autoregulatory response driven by increased neural activity in the inner retina. Little is known about flicker-induced changes of activity of retinal neurons themselves. We non-invasively investigated flicker-induced changes of retinal ganglion cell (RGC) function in common inbred mouse strains using the pattern electroretinogram (PERG), a sensitive measure of RGC function. Flicker was superimposed on the pattern stimulus at frequencies that did not generate measurable flicker-ERG and alter the PERG response. Transition from flicker at 101 Hz (control) to flicker at 11 Hz (test) at constant mean luminance induced a slow reduction of PERG amplitude to a minimum (39% loss in C57BL/6J mice and 52% loss in DBA/2J mice) 4–5 minutes after 11 Hz flicker onset, followed by a slow recovery to baseline over 20 minutes. Results demonstrate that the magnitude and temporal dynamics of RGC response induced by flicker at 11 Hz can be non-invasively assessed with PERG in the mouse. This allows investigating the functional phenotype of different mouse strains as well as pathological changes in glaucoma and optic nerve disease. The non-contact flicker-PERG method opens the possibility of combined assessment of neural and vascular response dynamics.

scholarly journals Systemic Treatment with Nicotinamide Riboside Is Protective in Two Mouse Models of Retinal Ganglion Cell Damage

Pharmaceutics ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 893
Author(s):  
Xian Zhang ◽  
Nan Zhang ◽  
Micah A. Chrenek ◽  
Preston E. Girardot ◽  
Jiaxing Wang ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Systemic Treatment ◽  
Cell Damage ◽  
Pattern Electroretinogram ◽  
Protective Effects ◽  
Retinal Ganglion ◽  
Independent Manner ◽  
Nerve Crush ◽  
Nicotinamide Riboside

Glaucoma etiology often includes retinal ganglion cell (RGC) death associated with elevated intraocular pressure (IOP). However, even when IOP is managed well, disease can progress. It is thus important to develop therapeutic approaches that directly protect RGCs in an IOP-independent manner. Compromised nicotinamide adenine dinucleotide (NAD+) metabolism occurs in neurodegenerative diseases, including models of glaucoma. Here we report testing the protective effects of prophylactically systemically administered nicotinamide riboside (NR), a NAD+ precursor, in a mouse model of acute RGC damage (optic nerve crush (ONC)), and in a chronic model of RGC degeneration (ocular hypertension induced by intracameral injection of microbeads). For both models, treatment enhanced RGC survival, assessed by counting cells in retinal flatmounts immunostained for Brn3a+. In the ONC model, treatment preserved RGC function, as assessed by pattern electroretinogram, and suppressed retinal inflammation, as assessed by immunofluorescence staining of retinal fixed sections for glial fibrillary acidic protein (GFAP). This is the first study to demonstrate that systemic treatment with NR is protective in acute and chronic models of RGC damage. The protection is significant and, considering that NR is highly bioavailable in and well-tolerated by humans, may support the proposition of prospective human subject studies.

scholarly journals Clinical electrophysiology of the optic nerve and retinal ganglion cells

Eye ◽  
2021 ◽  
Author(s):  
Oliver R. Marmoy ◽  
Suresh Viswanathan
Keyword(s):  
Optic Nerve ◽  
Ganglion Cell ◽  
Retinal Ganglion Cells ◽  
Retinal Ganglion Cell ◽  
Cell Function ◽  
Ganglion Cells ◽  
Pattern Electroretinogram ◽  
Photopic Negative Response ◽  
Clinical Electrophysiology ◽  
Retinal Ganglion

AbstractClinical electrophysiological assessment of optic nerve and retinal ganglion cell function can be performed using the Pattern Electroretinogram (PERG), Visual Evoked Potential (VEP) and the Photopic Negative Response (PhNR) amongst other more specialised techniques. In this review, we describe these electrophysiological techniques and their application in diseases affecting the optic nerve and retinal ganglion cells with the exception of glaucoma. The disease groups discussed include hereditary, compressive, toxic/nutritional, traumatic, vascular, inflammatory and intracranial causes for optic nerve or retinal ganglion cell dysfunction. The benefits of objective, electrophysiological measurement of the retinal ganglion cells and optic nerve are discussed, as are their applications in clinical diagnosis of disease, determining prognosis, monitoring progression and response to novel therapies.

Prenatal disruption of binocular interactions creates novel lamination in the cat's lateral geniculate nucleus

1988 ◽  
Vol 1 (1) ◽  
pp. 93-102 ◽  
Author(s):  
Preston E. Garraghty ◽  
Carla J. Shatz ◽  
Mriganka Sur
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Lateral Geniculate Nucleus ◽  
Retinal Ganglion ◽  
Monocular Enucleation ◽  
Lateral Geniculate ◽  
Binocular Interactions ◽  
Soma Size ◽  
Cell Layers ◽  
Normal Nucleus

AbstractThe elimination of retinogeniculate afferents from one eye on embryonic day 44 (E44) has pronounced effects on the formation of the cellular laminae in the cat lateral geniculate nucleus (LGN). Only two laminae form: a dorsal, “magnocellular” layer, and a ventral, “parvocellular” layer. Soma size measurements and previously reported patterns of termination of retinogeniculate axons suggest that the dorsal lamina is a coalescence of the normal A-laminae and the dorsal, magnocellular division of layer C, while the ventral layer is a composite of the parvocellular sublamina of layer C and the remaining C-laminae. This is a novel pattern of lamination in the LGN that differs from that found in the normal nucleus, not only in that there are now only two cell layers rather than the normal five, but also in that the interlaminar zone occurs in an abnormal location. This result is markedly different from that observed in other species where interlaminar zones present after early monocular enucleation are a subset of the ones which would normally be present. We suggest that, in the absence of ongoing binocular interactions, interactions between functionally distinct retinal ganglion cell classes from the remaining eye may direct the formation of cell laminae in the LGN, even when such interactions are not normally operative.

scholarly journals Retinal Neurodegeneration in db/db Mice at the Early Period of Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Qin Yang ◽  
Yidan Xu ◽  
Ping Xie ◽  
Haixia Cheng ◽  
Qinglu Song ◽  
...  
Keyword(s):  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Ganglion Cells ◽  
Early Period ◽  
Pattern Electroretinogram ◽  
Control Group ◽  
Retinal Ganglion ◽  
Fundus Fluorescein Angiography ◽  
Microvascular Changes ◽  
Diabetic Retina

Purpose.To describe both the functional and pathological alternations in neurosensory retina in a murine model of spontaneous type 2 diabetes (db/db mouse).Methods.db/db (BKS/DB−/−) mice and heterozygous littermates (as control group) at various ages (12, 16, 20, 24, and 28 weeks) were inspected with pattern electroretinogram (PERG), fundus fluorescein angiography (FFA), and optical coherence tomography (OCT). Histological markers of neuroinflammation (IBA-1 and F4/80) were evaluated by immunohistochemistry. In addition, levels of retinal ganglion cell death were measured by terminal dUTP nick-end labeling (TUNEL).Results.Significant alternations of PERG responses and increased retinal ganglion cells (RGCs) apoptosis were observed in diabetic db/db mice for 20-week period when compared with control group. IBA-1 and F4/80 expression in microglia/macrophages became evidently for 24-week period, thus supporting the PERG findings. Furthermore, obvious thinning of nasal and dorsal retina in 28-week-old db/db mice was also revealed by OCT. No visible retinal microvascular changes were detected by FFA throughout the experiments on db/db mice.Conclusions.Diabetic retina underwent neurodegenerative changes in db/db mice, which happened at retinal ganglion cell layer and inner nuclear layer. But there was no obvious abnormality in retinal vasculature on db/db mice.

scholarly journals Modeling Retinal Ganglion Cell Dysfunction in Optic Neuropathies

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1398
Author(s):  
Vittorio Porciatti ◽  
Tsung-Han Chou
Keyword(s):  
Cell Death ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Mouse Models ◽  
Time Course ◽  
Human Subjects ◽  
Pattern Electroretinogram ◽  
State Transitions ◽  
Retinal Ganglion ◽  
Response Dynamics

As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, the assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. RGC dysfunction can be assessed with the pattern electroretinogram (PERG), a sensitive measure of electrical activity of RGCs that is recorded non-invasively in human subjects and mouse models. Here, we offer a conceptual framework based on an intuitive state-transition model used for disease management in patients to identify progressive, potentially reversible stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies. We provide mathematical equations to describe state-transitions with a set of modifiable parameters that alter the time course and severity of state-transitions, which can be used for hypothesis testing and fitting experimental PERG data. PERG dynamics as a function of physiological stimuli are also used to differentiate phenotypic and altered RGC response dynamics, to assess susceptibility to stressors and to assess reversible dysfunction upon pharmacological treatment.

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