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J. P. Templeton, M. A. Nassr, F. R. Vazquez-Chona, W. E. Orr, R. W. Williams, E. E. Geisert; Differential Response of C57BL/6 and DBA/2J Mouse Retinas to Optic Nerve Crush. Invest. Ophthalmol. Vis. Sci. 2009;50(13):861.
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© ARVO (1962-2015); The Authors (2016-present)
Retinal ganglion cells in inbred mouse strains display different susceptibilities to injury. We examine this differential response using microarray techniques in the C57BL/6 and DBA/2J strains (the parental strains for the BXD recombinant inbred strain set). The long-term goal is to define the genetic networks modulating the susceptibility of ganglion cells to death.
The optic nerve of DBA/2J and C57BL/6 mice were crushed and the retinas were removed two and five days after crush. These samples were compared to control samples using the Illumina Sentrix Mouse-6V1 BeadChips. We identified 1582 genes with significant change in gene expression and grouped these changes into 5 functional groups using principal component (PC) analysis.
The first group (PC1) represents genes that change due to optic nerve crush. PC1 positive consists of genes related primarily to ganglion cell death and the negative component is made of genes involved in reactive gliosis and inflammation. The second group (PC2) is made of genes that are differentially expressed between the C57BL/6 and DBA/2J strains. The remaining three components represent interactions between the effects of optic nerve crush and genetic background. One component contains a differential response of crystallin genes. In the C57BL/6 mouse a subset of crystallin genes are down regulated over the 5 days after optic nerve crush, while in the DBA/2J mouse these same genes are up regulated. It is tempting to think of these changes as potentially underlying the differential response of the retina to injury.
This study demonstrates that there is a differential response in the retina between the C57BL/6 and DBA/2J strain. These changes in gene expression may underlie susceptibility and resistance of retinal ganglion cells to optic nerve crush. Future studies will map genomic loci modulating these differential responses using a retinal database of the BXD recombinant inbred strain set and analytical tools on GeneNetwork.org.
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