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Minzhong Yu, Neal S. Peachey, Preethi Ganapathy, Sylvia B. Smith; Age-related Changes In Visual Function In Cystathionine-beta-synthase Mutant Mice, A Model Of Hyperhomocysteinemia. Invest. Ophthalmol. Vis. Sci. 2011;52(14):704.
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Mice lacking cystathionine-beta-synthase (cbs-/-) have an excess of retinal homocysteine and develop abnormalities in multiple retinal layers, including photoreceptors and ganglion cells; heterozygous (cbs+/-) mice demonstrate ganglion cell loss (Ganapathy et al, 2009) and mitochondrial abnormalities in the optic nerve. How these alterations affect visual function in these mice is not known and was investigated in the present study.
Study mice were generated by breeding cbs+/- mice. Mice were studied at multiple ages (3, 5, 10, 15 weeks; 7, 12 months), using electroretinogram (ERG) protocols that allow the function of the outer neural retina and retinal pigment epithelium (RPE) to be examined, and using visual evoked potentials (VEPs) that monitor transmission through the visual pathway from retina to visual cortex.
ERG a- and b-waves of cbs-/- mice were significantly reduced at age 3 weeks. Responses of cbs+/- mice were not significantly different from WT (cbs+/+) until 7 months of age, where modest but significant reductions in ERG a- and b-waves were noted, as well as a selective reduction of the ERG light peak component, and delays in VEP implicit time.
Defects observed in cbs-/- mice correlate with the early onset of outer retinal abnormalities seen in the homozygous mutant. The late onset of functional defects in cbs+/- mice is consistent with a slow loss of photoreceptors and ganglion cells in the heterozygous mutant. Light peak abnormalities indicate that RPE function is also compromised in older cbs+/- heterozygotes.
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