Noninvasive Electroretinographic Procedures for the Study of the Mouse Retina

Kinoshita, Junzo; Peachey, Neal S.

doi:10.1002/cpmo.39

Cited by 33 publications

(29 citation statements)

References 51 publications

(71 reference statements)

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“…In most cases, we used a 500 ms recording epoch. To examine the ERG c-wave, we recorded responses for 4 s duration ( Kinoshita and Peachey, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Microtubule-Associated Protein 1 Light Chain 3B, (LC3B) Is Necessary to Maintain Lipid-Mediated Homeostasis in the Retinal Pigment Epithelium

Dhingra

Bell

Peachey

et al. 2018

Front. Cell. Neurosci.

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Like other neurons, retinal cells utilize autophagic pathways to maintain cell homeostasis. The mammalian retina relies on heterophagy and selective autophagy to efficiently degrade and metabolize ingested lipids with disruption in autophagy associated degradation contributing to age related retinal disorders. The retinal pigment epithelium (RPE) supports photoreceptor cell renewal by daily phagocytosis of shed photoreceptor outer segments (OS). The daily ingestion of these lipid-rich OS imposes a constant degradative burden on these terminally differentiated cells. These cells rely on Microtubule-Associated Protein 1 Light Chain 3 (LC3) family of proteins for phagocytic clearance of the ingested OS. The LC3 family comprises of three highly homologous members, MAP1LC3A (LC3A), MAP1LC3B (LC3B), and MAP1LC3C (LC3C). The purpose of this study was to determine whether the LC3B isoform plays a specific role in maintaining RPE lipid homeostasis. We examined the RPE and retina of the LC3B-/- mouse as a function of age using in vivo ocular imaging and electroretinography coupled with ex vivo, lipidomic analyses of lipid mediators, assessment of bisretinoids as well as imaging of lipid aggregates. Deletion of LC3B resulted in defects within the RPE including increased phagosome accumulation, decreased fatty acid oxidation and a subsequent increase in RPE and sub-RPE lipid deposits. Age-dependent RPE changes included elevated levels of oxidized cholesterol, deposition of 4-HNE lipid peroxidation products, bisretinoid lipofuscin accumulation, and subretinal migration of microglia, collectively likely contributing to loss of retinal function. These observations are consistent with a critical role for LC3B-dependent processes in the maintenance of normal lipid homeostasis in the aging RPE, and suggest that LC3 isoform specific disruption in autophagic processes contribute to AMD-like pathogenesis.

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“…In most cases, we used a 500 ms recording epoch. To examine the ERG c-wave, we recorded responses for 4 s duration ( Kinoshita and Peachey, 2018 ).…”

Section: Methodsmentioning

confidence: 99%

Microtubule-Associated Protein 1 Light Chain 3B, (LC3B) Is Necessary to Maintain Lipid-Mediated Homeostasis in the Retinal Pigment Epithelium

Dhingra

Bell

Peachey

et al. 2018

Front. Cell. Neurosci.

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“…****P < 0.0001. from flash onset to the a-wave trough and b-wave implicit time from flash onset to b-wave maximal amplitude, all according to previous literature describing ERG measurements. 39 Final data was retrieved from averaging left and right eye. 40 Electroretinograms (Figs.…”

Section: Electroretinographymentioning

confidence: 99%

“…Representative electroretinograms are shown for nondiabetic (black) and diabetic (red) animals. Measurements were performed as described in Kinoshita & Peachey 39. Amplitudes of a-and b-wave declined early after development of diabetes in the STZ-treated mice compared to control mice, while the latency and implicit times increased over time.…”

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confidence: 99%

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Sergeys

Étienne

Hove

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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The goal of this study was to perform an extensive temporal characterization of the early pathologic processes in the streptozotocin (STZ)-induced diabetic retinopathy (DR) mouse model, beyond the vascular phenotype, and to investigate the potential of clinically relevant compounds in attenuating these processes. METHODS. Visual acuity and contrast sensitivity (CS) were studied in the mouse STZ model until 24 weeks postdiabetes onset. ERG, spectral domain optical coherence tomography (SD-OCT), leukostasis, and immunohistochemistry were applied to investigate neurodegeneration, inflammation, and gliosis during early-, mid-and late-phase diabetes. Aflibercept or triamcinolone acetonide (TAAC) was administered to investigate their efficacy on the aforementioned processes. RESULTS. Visual acuity and CS loss started at 4 and 18 weeks postdiabetes onset, respectively, and progressively declined over time. ERG amplitudes were diminished and OP latencies increased after 6 weeks, whereas SD-OCT revealed retinal thinning from 4 weeks postdiabetes. Immunohistochemical analyses linked these findings to retinal ganglion and cholinergic amacrine cell loss at 4 and 8 weeks postdiabetes onset, respectively, which was further decreased after aflibercept administration. The number of adherent leukocytes was augmented after 2 weeks, whereas increased micro-and macroglia reactivity was present from 4 weeks postdiabetes. Aflibercept or TAAC showed improved efficacy on inflammation and gliosis. CONCLUSIONS. STZ-induced diabetic mice developed early pathologic DR hallmarks, from which inflammation seemed the initial trigger, leading to further development of functional and morphologic retinal changes. These findings indicate that the mouse STZ model is suitable to study novel integrative non-vascular therapies to treat early DR.

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“…We used standard light- 45 and dark-adapted 46 protocols based on ISCEV standards. For the light-adapted protocol, 4-ms green flashes of 9 incrementing steps ranging from 0.16 to 30 cd•s/m 2 were presented on a green rodsuppressing background of 30 cd/m 2 and adapted for 10 minutes prior to recording.…”

Section: Stimulation and Recordingmentioning

confidence: 99%

“…40 The a-wave is followed by the b-wave, which is a corneal-positive potential originating from bipolar cells. 40,[43][44][45][46] The b-wave response has been attributed to Müller glial cells. However, examina-tion of mice where Müller cells were functionally inactivated resulted in no change in the b-wave, suggesting that they are not involved.…”

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confidence: 99%

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

Jimenez

Lines

Kueppers

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-Daspartate receptor (NMDAR) hypofunction in subjects with schizophrenia shows great potential. We report the first fERG study in a genetic mouse model of schizophrenia characterized by NMDAR hypofunction from gene silencing of serine racemase (SR) expression (SR-/-), an established risk gene for schizophrenia. We analyzed fERG parameters under various background light adaptations to determine the most significant variables to allow for early identification of people at risk for schizophrenia, prior to onset of psychosis. SR is a risk gene for schizophrenia, and negative and cognitive symptoms antedate the onset of psychosis that is required for diagnosis. METHODS. The scotopic, photopic, and mesopic fERGs were analyzed in male and female mice in both SR-/and wild-type (WT) mice and also analyzed for sex differences. Amplitude and implicit time of the a-and b-wave components, b-/a-wave ratio, and Fourier transform analysis were analyzed. RESULTS. Mesopic a-and b-wave implicit times were significantly delayed, and b-wave amplitudes, b/a ratios, and Fourier transform were significantly decreased in the male SR-/mice compared to WT, but not in female SR-/mice. No significant differences were observed in photopic or scotopic fERGs between genotype. CONCLUSIONS. The fERG prognostic capability may be improved by examination of background light adaptation, a larger array of light intensities, considering sex as a variable, and performing Fourier transform analyses of all waveforms. This should improve the ability to differentiate between controls and subjects with schizophrenia characterized by NMDAR hypofunction.

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Noninvasive Electroretinographic Procedures for the Study of the Mouse Retina

Cited by 33 publications

References 51 publications

Microtubule-Associated Protein 1 Light Chain 3B, (LC3B) Is Necessary to Maintain Lipid-Mediated Homeostasis in the Retinal Pigment Epithelium

Microtubule-Associated Protein 1 Light Chain 3B, (LC3B) Is Necessary to Maintain Lipid-Mediated Homeostasis in the Retinal Pigment Epithelium

Longitudinal In Vivo Characterization of the Streptozotocin-Induced Diabetic Mouse Model: Focus on Early Inner Retinal Responses

Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis

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