The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell Function in Patients With Leber's Hereditary Optic Neuropathy

Karanjia, Rustum; Berezovsky, Adriana; Sacai, Paula Yuri; Cavascan, Nívea Nunes; Liu, Henry Yuheng; Nazarali, Samir; Moraes-Filho, Milton N.; Anderson, Kirsten; Tran, Justin; Watanabe, Sung Eun Song; Moraes, Maria Nathália; Sadun, Federico; DeNegri, Anna Maria; Barboni, Piero; Ramos, Carolina do Val Ferreira; Morgia, Chiara La; Carelli, Valerio; Belfort, Rubens; Coupland, Stuart G.; Salomão, Solange Rios; Sadun, Alfredo A.

doi:10.1167/iovs.17-21773

Cited by 25 publications

(16 citation statements)

References 24 publications

(28 reference statements)

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“…Differences in RGC viability were reflected by differences in RGC-dependent retinal function as analyzed by ERG. As in previous studies 29 , IOP-induced ischemia led to a significant decline in the PhNR, a component of the full-field flash ERG specific for RGC-dependent retinal activity 30 . MBV injections prevented the IOP-induced loss in PhNR similar to previous studies using stem cell-derived exosomes 31 .…”

Section: Discussionsupporting

confidence: 77%

Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function

Merwe

Faust

Sakalli

et al. 2019

Sci Rep

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Injury to retinal ganglion cells (RGC), central nervous system neurons that relay visual information to the brain, often leads to RGC axon degeneration and permanently lost visual function. Herein this study shows matrix-bound nanovesicles (MBV), a distinct class of extracellular nanovesicle localized specifically to the extracellular matrix (ECM) of healthy tissues, can neuroprotect RGCs and preserve visual function after severe, intraocular pressure (IOP) induced ischemia in rat. Intravitreal MBV injections attenuated IOP-induced RGC axon degeneration and death, protected RGC axon connectivity to visual nuclei in the brain, and prevented loss in retinal function as shown by histology, anterograde axon tracing, manganese-enhanced magnetic resonance imaging, and electroretinography. In the optic nerve, MBV also prevented IOP-induced decreases in growth associated protein-43 and IOP-induced increases in glial fibrillary acidic protein. In vitro studies showed MBV suppressed pro-inflammatory signaling by activated microglia and astrocytes, stimulated RGC neurite growth, and neuroprotected RGCs from neurotoxic media conditioned by pro-inflammatory astrocytes. Thus, MBV can positively modulate distinct signaling pathways (e.g., inflammation, cell death, and axon growth) in diverse cell types. Since MBV are naturally derived, bioactive factors present in numerous FDA approved devices, MBV may be readily useful, not only experimentally, but also clinically as immunomodulatory, neuroprotective factors for treating trauma or disease in the retina as well as other CNS tissues.

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Section: Discussionsupporting

confidence: 77%

Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function

Merwe

Faust

Sakalli

et al. 2019

Sci Rep

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“…We asked the question of whether the efficacy of FAs on RGC survival was associated with ameliorated retinal function by analyzing the amplitude of the PhNR, a sensitive marker of the inner retinal function [ 25 , 26 , 27 ]. PhNR amplitude is altered in several retinal pathologies involving RGCs and including, among others, glaucoma, diabetic optic nerve atrophy, and optic neuritis [ 12 ]. The amplitude of the PhNR is proportional to the number of functional RGCs [ 28 , 29 , 30 , 31 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

“…In addition, we determined how FAs-induced rescue of RGC death may be related to ameliorated optic nerve histopathology by performing ultrastructural morphometric analysis by transmission electron microscopy. Finally, we aimed at correlating RGC rescue with visual function by determining the effect of FAs on the photopic negative response (PhNR) of an electroretinogram (ERG), an efficient tool to unravel the role of RGCs in the generation of electroretinographic waves [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

Further Evidence on Efficacy of Diet Supplementation with Fatty Acids in Ocular Pathologies: Insights from the EAE Model of Optic Neuritis

et al. 2018

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In the experimental autoimmune encephalomyelitis (EAE) mouse model of optic neuritis, we recently demonstrated that diet supplementation with a balanced mixture of fatty acids (FAs), including omega 3 and omega 6, efficiently limited inflammatory events in the retina and prevented retinal ganglion cell (RGC) death, although mechanisms underlying the efficacy of FAs were to be elucidated. Whether FAs effectiveness was accompanied by efficient rescue of demyelinating events in the optic nerve was also unresolved. Finally, the possibility that RGC rescue might result in ameliorated visual performance remained to be investigated. Here, the EAE model of optic neuritis was used to investigate mechanisms underlying the anti-inflammatory effects of FAs, including their potential efficacy on macrophage polarization. In addition, we determined how FAs-induced rescue of RGC degeneration was related to optic nerve histopathology by performing ultrastructural morphometric analysis with transmission electron microscopy. Finally, RGC rescue was correlated with visual performance by recording photopic electroretinogram, an efficient methodology to unravel the role of RGCs in the generation of electroretinographic waves. We conclude that the ameliorative effects of FAs were dependent on a predominant anti-inflammatory action including a role on promoting the shift of macrophages from the inflammatory M1 phenotype towards the anti-inflammatory M2 phenotype. This would finally result in restored optic nerve histopathology and ameliorated visual performance. These findings can now offer new perspectives for implementing our knowledge on the effectiveness of diet supplementation in counteracting optic neuritis and suggest the importance of FAs as possible adjuvants in therapies against inflammatory diseases of the eye.

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“…PhNR amplitude has been found to be reduced in many pathological conditions including glaucomatous optic neuropathy [ 43 ], ocular hypertension [ 18 , 30 , 44 , 45 ], Leber hereditary optic neuropathy [ 46 ], optic nerve atrophy [ 47 ], diabetic retinopathy [ 48 ], central retinal artery occlusion [ 49 ] and idiopathic endocranial hypertension [ 50 , 51 ]. After having established that the red-on-blue (R/B) stimulation gives more discriminating results than white-on-white (W/W) stimulation in detecting glaucomatous damage [ 20 , 21 ], we now present the most interesting experiences in the field.…”

Section: Measuring the Phnr: Clinical Experiencesmentioning

confidence: 99%

The photopic negative response (PhNR): measurement approaches and utility in glaucoma

et al. 2020

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Purpose Visual electrophysiological testing continues to generate interest among glaucoma experts because of its potential help in clarifying disease pathophysiology and promoting early detection of glaucomatous damage. The photopic negative response (PhNR) is a slow negative component of the full-field electroretinogram that has been shown to provide specific information about retinal ganglion cells (RGCs) activity. The purpose of this article is to review the literature to explore the currently available measurement methods and the utility of PhNR in glaucoma diagnostic process. Methods We gathered publications related to the origins, types of stimuli used, measurements methods and applications of the PhNR of ERG in animal models and humans through a search of the literature cited in PubMed. Search terms were: ''PhNR'', ''photopic negative response'', ''glaucoma'', ''glaucomatous optic neuropathy'', ''ERG'', ''electroretinogram''. Results The most reliable PhNR measurements are obtained using a red stimulus on a blue background,

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The Photopic Negative Response: An Objective Measure of Retinal Ganglion Cell Function in Patients With Leber's Hereditary Optic Neuropathy

Cited by 25 publications

References 24 publications

Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function

Matrix-bound nanovesicles prevent ischemia-induced retinal ganglion cell axon degeneration and death and preserve visual function

Further Evidence on Efficacy of Diet Supplementation with Fatty Acids in Ocular Pathologies: Insights from the EAE Model of Optic Neuritis

The photopic negative response (PhNR): measurement approaches and utility in glaucoma

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