Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia

Minzhong Yu, Gwen Sturgill-Short, Preethi Ganapathy, Amany Mohamed Tawfik, Neal S. Peachey, Sylvia B Smith

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs -/-) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs +/-) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs -/- (3 weeks) and cbs +/- mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs -/- mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs +/- mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs +/- mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs +/- mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs +/- mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs +/- mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalExperimental eye research
Volume96
Issue number1
DOIs
StatePublished - Mar 1 2012

Fingerprint

Cystathionine beta-Synthase
Hyperhomocysteinemia
Homocysteine
Retinal Pigments
Visual Evoked Potentials
Ganglia
Light
Multiple Abnormalities
Retinal Diseases
Optic Nerve Diseases
Photoreceptor Cells
Visual Cortex
Optic Nerve
Methionine
Glaucoma
Cardiovascular Diseases

Keywords

  • Electrophysiology
  • Electroretinogram
  • Mouse
  • Optic nerve
  • Retina
  • Retinal degeneration
  • Retinal function
  • Visual evoked potential

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia. / Yu, Minzhong; Sturgill-Short, Gwen; Ganapathy, Preethi; Tawfik, Amany Mohamed; Peachey, Neal S.; Smith, Sylvia B.

In: Experimental eye research, Vol. 96, No. 1, 01.03.2012, p. 124-131.

Research output: Contribution to journalArticle

Yu, Minzhong ; Sturgill-Short, Gwen ; Ganapathy, Preethi ; Tawfik, Amany Mohamed ; Peachey, Neal S. ; Smith, Sylvia B. / Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia. In: Experimental eye research. 2012 ; Vol. 96, No. 1. pp. 124-131.
@article{3c842ff88be04fc9af4df69bc14da149,
title = "Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia",
abstract = "Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs -/-) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs +/-) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs -/- (3 weeks) and cbs +/- mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs -/- mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs +/- mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs +/- mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs +/- mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs +/- mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs +/- mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.",
keywords = "Electrophysiology, Electroretinogram, Mouse, Optic nerve, Retina, Retinal degeneration, Retinal function, Visual evoked potential",
author = "Minzhong Yu and Gwen Sturgill-Short and Preethi Ganapathy and Tawfik, {Amany Mohamed} and Peachey, {Neal S.} and Smith, {Sylvia B}",
year = "2012",
month = "3",
day = "1",
doi = "10.1016/j.exer.2011.12.011",
language = "English (US)",
volume = "96",
pages = "124--131",
journal = "Experimental Eye Research",
issn = "0014-4835",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Age-related changes in visual function in cystathionine-beta-synthase mutant mice, a model of hyperhomocysteinemia

AU - Yu, Minzhong

AU - Sturgill-Short, Gwen

AU - Ganapathy, Preethi

AU - Tawfik, Amany Mohamed

AU - Peachey, Neal S.

AU - Smith, Sylvia B

PY - 2012/3/1

Y1 - 2012/3/1

N2 - Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs -/-) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs +/-) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs -/- (3 weeks) and cbs +/- mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs -/- mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs +/- mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs +/- mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs +/- mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs +/- mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs +/- mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.

AB - Homocysteine is an amino acid required for the metabolism of methionine. Excess homocysteine is implicated in cardiovascular and neurological disease and new data suggest a role in various retinopathies. Mice lacking cystathionine-beta-synthase (cbs -/-) have an excess of retinal homocysteine and develop anatomical abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs +/-) mice demonstrate ganglion cell loss and mitochondrial abnormalities in the optic nerve. The purpose of the present study was to determine whether elevated homocysteine, due to absent or diminished cbs, alters visual function. We examined cbs -/- (3 weeks) and cbs +/- mice (5, 10, 15, 30 weeks) and results were compared to those obtained from wild type (WT) littermates. Conventional dark- and light-adapted ERGs were recorded, along with dc-ERG to assess retinal pigment epithelial (RPE) function. The visual evoked potential (VEP) was used to assess transmission to the visual cortex. The amplitudes of the major ERG components were reduced in cbs -/- mice at age 3 weeks and VEPs were delayed markedly. These findings are consistent with the early retinal disruption observed anatomically in these mice. In comparison, at 3 weeks of age, responses of cbs +/- mice did not differ significantly from those of WT mice. Functional abnormalities were not observed in cbs +/- mice until 15 weeks of age, at which time amplitude reductions were noted for the ERG a- and b-wave and the light peak component, but not for other components generated by the RPE. VEP implicit times were delayed in cbs +/- mice at 15 and 30 weeks, while VEP amplitudes were unaffected. The later onset of functional defects in cbs +/- mice is consistent with a slow loss of ganglion cells reported previously in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs +/- mice. The data suggest that severe elevations of homocysteine are associated with marked alterations of retinal function while modest homocysteine elevation is reflected in milder and delayed alterations of retinal function. The work lays the foundation to explore the role of homocysteine in retinal diseases such as glaucoma and optic neuropathy.

KW - Electrophysiology

KW - Electroretinogram

KW - Mouse

KW - Optic nerve

KW - Retina

KW - Retinal degeneration

KW - Retinal function

KW - Visual evoked potential

UR - http://www.scopus.com/inward/record.url?scp=84862803353&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862803353&partnerID=8YFLogxK

U2 - 10.1016/j.exer.2011.12.011

DO - 10.1016/j.exer.2011.12.011

M3 - Article

C2 - 22197750

AN - SCOPUS:84862803353

VL - 96

SP - 124

EP - 131

JO - Experimental Eye Research

JF - Experimental Eye Research

SN - 0014-4835

IS - 1

ER -