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

Nathalia Torres Jimenez; Justin W. Lines; Rachel B. Kueppers; Paulo Kofuji; Henry Wei; Amy Rankila; Joseph T. Coyle; Robert F. Miller; Linda K. McLoon

doi:10.1167/iovs.61.2.16

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

Nathalia Torres Jimenez, Justin W. Lines, Rachel B. Kueppers, Paulo Kofuji, Henry Wei, Amy Rankila, Joseph T. Coyle, Robert F. Miller, Linda K. McLoon

Research output: Contribution to journal › Article › peer-review

4 Scopus citations

Abstract

Purpose: Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-d-aspartate 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.

Original language	English (US)
Article number	16
Number of pages	1
Journal	Investigative ophthalmology & visual science
Volume	61
Issue number	2
DOIs	https://doi.org/10.1167/iovs.61.2.16
State	Published - Feb 7 2020

Bibliographical note

Funding Information:
Supported by National Institutes of Health Grants 1F31MH106296-01 (NTJ), 1F31AG057155-01A1 (JWL), R01 EY15313 (LKM), R21 EY025027 (RFM), T32 EY025187, and P30 EY11375; Office of the Vice President for Research (NTJ); and the Minnesota Lions Foundation.

Publisher Copyright:
Copyright 2020 The Authors.

PubMed: MeSH publication types

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Publisher link

10.1167/iovs.61.2.16

Find It

Find It at U of M Libraries

Cite this

Jimenez, N. T., Lines, J. W., Kueppers, R. B., Kofuji, P., Wei, H., Rankila, A., Coyle, J. T., Miller, R. F., & McLoon, L. K. (2020). Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia: A and B Wave Analysis. Investigative ophthalmology & visual science, 61(2), Article 16. https://doi.org/10.1167/iovs.61.2.16

@article{e9b32b19174f40cb9ddf4f7634ce67f7,

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

abstract = "Purpose: Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-d-aspartate 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.",

author = "Jimenez, {Nathalia Torres} and Lines, {Justin W.} and Kueppers, {Rachel B.} and Paulo Kofuji and Henry Wei and Amy Rankila and Coyle, {Joseph T.} and Miller, {Robert F.} and McLoon, {Linda K.}",

note = "Funding Information: Supported by National Institutes of Health Grants 1F31MH106296-01 (NTJ), 1F31AG057155-01A1 (JWL), R01 EY15313 (LKM), R21 EY025027 (RFM), T32 EY025187, and P30 EY11375; Office of the Vice President for Research (NTJ); and the Minnesota Lions Foundation. Publisher Copyright: Copyright 2020 The Authors.",

year = "2020",

month = feb,

day = "7",

doi = "10.1167/iovs.61.2.16",

language = "English (US)",

volume = "61",

journal = "Investigative ophthalmology & visual science",

issn = "0146-0404",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "2",

}

TY - JOUR

T1 - Electroretinographic Abnormalities and Sex Differences Detected with Mesopic Adaptation in a Mouse Model of Schizophrenia

T2 - A and B Wave Analysis

AU - Jimenez, Nathalia Torres

AU - Lines, Justin W.

AU - Kueppers, Rachel B.

AU - Kofuji, Paulo

AU - Wei, Henry

AU - Rankila, Amy

AU - Coyle, Joseph T.

AU - Miller, Robert F.

AU - McLoon, Linda K.

N1 - Funding Information: Supported by National Institutes of Health Grants 1F31MH106296-01 (NTJ), 1F31AG057155-01A1 (JWL), R01 EY15313 (LKM), R21 EY025027 (RFM), T32 EY025187, and P30 EY11375; Office of the Vice President for Research (NTJ); and the Minnesota Lions Foundation. Publisher Copyright: Copyright 2020 The Authors.

PY - 2020/2/7

Y1 - 2020/2/7

N2 - Purpose: Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-d-aspartate 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.

AB - Purpose: Mesopic flash electroretinography (fERG) as a tool to identify N-methyl-d-aspartate 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.

UR - http://www.scopus.com/inward/record.url?scp=85079334701&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85079334701&partnerID=8YFLogxK

U2 - 10.1167/iovs.61.2.16

DO - 10.1167/iovs.61.2.16

M3 - Article

C2 - 32053730

SN - 0146-0404

VL - 61

JO - Investigative ophthalmology & visual science

JF - Investigative ophthalmology & visual science

IS - 2

M1 - 16

ER -

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

Abstract

Bibliographical note

PubMed: MeSH publication types

Publisher link

Find It

Other files and links

Fingerprint

Cite this