Skip to main content
Top
Published in: Documenta Ophthalmologica 3/2017

01-06-2017 | Original Research Article

Detailed electroretinographic findings in rd8 mice

Authors: Alan B. Saul, Xuezhi Cui, Shanu Markand, Sylvia B. Smith

Published in: Documenta Ophthalmologica | Issue 3/2017

Login to get access

Abstract

Purpose

Previous work has suggested that the retinal degeneration mutant rd8 mouse lacks an electroretinographic (ERG) phenotype until about 9 months of age. We evaluated the ERG phenotype of these mice by measuring both conventional ERG responses and scotopic threshold responses.

Methods

Groups of 4-month-old wild-type (WT) and mutant (rd8) mice were anesthetized and tested for mass retinal responses (ERGs) to several types of visual stimuli. Scotopic threshold responses were accumulated with brief scotopic flashes at a series of very dim intensities. Dark-adapted (scotopic) and light-adapted (photopic) responses to brief flashes at a series of higher intensities were recorded, along with long flashes and random modulations of light levels under photopic conditions.

Results

Negative scotopic threshold responses (nSTRs) had lower amplitudes in rd8 mice compared to WTs. Positive scotopic threshold responses were similar in the two groups. With the more intense stimuli, a- and c-wave amplitudes were smaller in rd8 mice. Both scotopic and photopic b-wave amplitudes tended to be larger in rd8 mice, though generally not significantly.

Conclusions

The striking decrease in nSTR amplitudes was surprising, given that the main retinal effects of the rd8 mutation occur in the outer retina, at the external limiting membrane. The primary source of nSTRs in mice is thought to be at the amacrine cell level in the inner retina. Investigation of how this mutation leads to inner retinal dysfunction might reveal unexpected aspects of retinal cell biology and circuitry.
Literature
3.
go back to reference Mehalow AK, Kameya S, Smith RS, Hawes NL, Denegre JM, Young JA, Bechtold L, Haider NB, Tepass U, Heckenlively JR, Chang B, Naggert JK, Nishina PM (2003) CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet 12:2179–2189. doi:10.1093/hmg/ddg232 CrossRefPubMed Mehalow AK, Kameya S, Smith RS, Hawes NL, Denegre JM, Young JA, Bechtold L, Haider NB, Tepass U, Heckenlively JR, Chang B, Naggert JK, Nishina PM (2003) CRB1 is essential for external limiting membrane integrity and photoreceptor morphogenesis in the mammalian retina. Hum Mol Genet 12:2179–2189. doi:10.​1093/​hmg/​ddg232 CrossRefPubMed
4.
go back to reference Zhao M, Andrieu-Soler C, Kowalczuk L, Paz Cortés M, Berdugo M, Dernigoghossian M, Halili F, Jeanny J-C, Goldenberg B, Savoldelli M, El Sanharawi M, Naud M-C, van Ijcken W, Pescini-Gobert R, Martinet D, Maass A, Wignholds J, Crisanti P, Rivolta C, Behar-Cohen F (2015) A new CRB1 rat mutation links Muller glial cells to retinal telangiectasia. J Neurosci 35:6093–6106. doi:10.1523/JNEUROSCI.3412-14.2015 CrossRefPubMedPubMedCentral Zhao M, Andrieu-Soler C, Kowalczuk L, Paz Cortés M, Berdugo M, Dernigoghossian M, Halili F, Jeanny J-C, Goldenberg B, Savoldelli M, El Sanharawi M, Naud M-C, van Ijcken W, Pescini-Gobert R, Martinet D, Maass A, Wignholds J, Crisanti P, Rivolta C, Behar-Cohen F (2015) A new CRB1 rat mutation links Muller glial cells to retinal telangiectasia. J Neurosci 35:6093–6106. doi:10.​1523/​JNEUROSCI.​3412-14.​2015 CrossRefPubMedPubMedCentral
5.
go back to reference Jacobson SG, Cideciyan AV, Aleman TS, Pianta MJ, Sumaroka A, Schwartz SB, Smilko EE, Milam AH, Sheffield VC, Stone EM (2003) Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum Mol Genet 12:1073–1078CrossRefPubMed Jacobson SG, Cideciyan AV, Aleman TS, Pianta MJ, Sumaroka A, Schwartz SB, Smilko EE, Milam AH, Sheffield VC, Stone EM (2003) Crumbs homolog 1 (CRB1) mutations result in a thick human retina with abnormal lamination. Hum Mol Genet 12:1073–1078CrossRefPubMed
6.
go back to reference Mattapallil MJ, Wawrousek EF, Chan C-C, Zhao H, Roychoudhury J, Ferguson TA, Caspi RR (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6 N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53:2921–2927. doi:10.1167/iovs.12-9662 CrossRefPubMedPubMedCentral Mattapallil MJ, Wawrousek EF, Chan C-C, Zhao H, Roychoudhury J, Ferguson TA, Caspi RR (2012) The Rd8 mutation of the Crb1 gene is present in vendor lines of C57BL/6 N mice and embryonic stem cells, and confounds ocular induced mutant phenotypes. Invest Ophthalmol Vis Sci 53:2921–2927. doi:10.​1167/​iovs.​12-9662 CrossRefPubMedPubMedCentral
7.
go back to reference Lawrance AK, Racine J, Deng L, Wang X, Lachapelle P, Rozen R (2011) Complete deficiency of methylenetetrahydrofolate reductase in mice is associated with impaired retinal function and variable mortality, hematological profiles, and reproductive outcomes. J Inherit Metab Dis 34:147–157. doi:10.1007/s10545-010-9127-1 CrossRefPubMed Lawrance AK, Racine J, Deng L, Wang X, Lachapelle P, Rozen R (2011) Complete deficiency of methylenetetrahydrofolate reductase in mice is associated with impaired retinal function and variable mortality, hematological profiles, and reproductive outcomes. J Inherit Metab Dis 34:147–157. doi:10.​1007/​s10545-010-9127-1 CrossRefPubMed
8.
go back to reference Markand S, Saul A, Roon P, Prasad P, Martin P, Rozen R, Ganapaty V, Smith SB (2015) Retinal ganglion cell loss and mild vasculopathy in methylene tetrahydrofolate reductase (Mthfr) deficient mice: a model of mild hyperhomocysteinemia. Invest Ophthalmol Vis Sci 56:2684–2695. doi:10.1167/iovs.14-16190 CrossRefPubMedPubMedCentral Markand S, Saul A, Roon P, Prasad P, Martin P, Rozen R, Ganapaty V, Smith SB (2015) Retinal ganglion cell loss and mild vasculopathy in methylene tetrahydrofolate reductase (Mthfr) deficient mice: a model of mild hyperhomocysteinemia. Invest Ophthalmol Vis Sci 56:2684–2695. doi:10.​1167/​iovs.​14-16190 CrossRefPubMedPubMedCentral
10.
go back to reference Aleman TS, Cideciyan AV, Aguirre GK, Huang WC, Mullins CL, Roman AJ, Sumaroka A, Olivares MB, Tsai FF, Schwartz SB, Vandenberghe LH, Limberis MP, Stone EM, Bell P, Wilson JM, Jacobson SG (2011) Human CRB1-associated retinal degeneration: comparison with the rd8 Crb1-mutant mouse model. Invest Ophthalmol Vis Sci 52:6898–6910. doi:10.1167/iovs.11-7701 CrossRefPubMedPubMedCentral Aleman TS, Cideciyan AV, Aguirre GK, Huang WC, Mullins CL, Roman AJ, Sumaroka A, Olivares MB, Tsai FF, Schwartz SB, Vandenberghe LH, Limberis MP, Stone EM, Bell P, Wilson JM, Jacobson SG (2011) Human CRB1-associated retinal degeneration: comparison with the rd8 Crb1-mutant mouse model. Invest Ophthalmol Vis Sci 52:6898–6910. doi:10.​1167/​iovs.​11-7701 CrossRefPubMedPubMedCentral
11.
go back to reference Sieving PA, Frishman LJ, Steinberg RH (1986) Scotopic threshold response of proximal retina in cat. J Neurophysiol 56:1049–1061PubMed Sieving PA, Frishman LJ, Steinberg RH (1986) Scotopic threshold response of proximal retina in cat. J Neurophysiol 56:1049–1061PubMed
12.
13.
go back to reference Frishman LJ (2006) Origins of the electroretinogram. In: Heckenlively JR, Arden GB (eds) Principles and practice of clinical electrophysiology of vision, 2nd edn. MIT Press, Cambridge, pp 139–183 Frishman LJ (2006) Origins of the electroretinogram. In: Heckenlively JR, Arden GB (eds) Principles and practice of clinical electrophysiology of vision, 2nd edn. MIT Press, Cambridge, pp 139–183
14.
go back to reference Oakley B, Green DG (1976) Correlation of light-induced changes in retinal extracellular potassium concentration with c-wave of the electroretinogram. J Neurophysiol 39:1117–1133PubMed Oakley B, Green DG (1976) Correlation of light-induced changes in retinal extracellular potassium concentration with c-wave of the electroretinogram. J Neurophysiol 39:1117–1133PubMed
15.
go back to reference Yanase J, Ogawa H (1997) Effects of halothane and sevoflurane on the electroretinogram of dogs. Am J Veterinary Res 58:904–909 Yanase J, Ogawa H (1997) Effects of halothane and sevoflurane on the electroretinogram of dogs. Am J Veterinary Res 58:904–909
17.
go back to reference Luhmann UF, Carvalho LS, Kleine Holthaus SM, Cowing JA, Greenaway S, Chu CJ, Ali RR (2015) The severity of retinal pathology in homozygous CRB1rd8/rd8 mice is dependent on additional genetic factors. Hum Mol Genet 24:128–141. doi:10.1093/hmg/ddu424 CrossRefPubMed Luhmann UF, Carvalho LS, Kleine Holthaus SM, Cowing JA, Greenaway S, Chu CJ, Ali RR (2015) The severity of retinal pathology in homozygous CRB1rd8/rd8 mice is dependent on additional genetic factors. Hum Mol Genet 24:128–141. doi:10.​1093/​hmg/​ddu424 CrossRefPubMed
20.
go back to reference Frishman LJ, Steinberg RH (1989) Intraretinal analysis of the threshold dark-adapted ERG of cat retina. J Neurophysiol 61:1221–1232PubMed Frishman LJ, Steinberg RH (1989) Intraretinal analysis of the threshold dark-adapted ERG of cat retina. J Neurophysiol 61:1221–1232PubMed
Metadata
Title
Detailed electroretinographic findings in rd8 mice
Authors
Alan B. Saul
Xuezhi Cui
Shanu Markand
Sylvia B. Smith
Publication date
01-06-2017
Publisher
Springer Berlin Heidelberg
Published in
Documenta Ophthalmologica / Issue 3/2017
Print ISSN: 0012-4486
Electronic ISSN: 1573-2622
DOI
https://doi.org/10.1007/s10633-017-9585-y

Other articles of this Issue 3/2017

Documenta Ophthalmologica 3/2017 Go to the issue