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F. Vazquez–Chona, L. Lu, E.J. Chesler, R. Williams, E.E. Geisert; Common gene expression and regulation following injury in the retina, brain, and spinal cord . Invest. Ophthalmol. Vis. Sci. 2004;45(13):4674.
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Purpose: The response of the mammalian retina to injury is similar to that occurring in other parts of the central nervous system (CNS). Like the brain and spinal cord, the retina contains glial cells which display a reactive response after injury. The astrocytes and Muller cells can hypertrophy, proliferate and migrate, leading eventually to the formation of a glial scar. This study brings together gene expression and genetic studies to identify regions of the mouse genome regulating changes in gene expression that occur following injury in the CNS. Methods: The first aspect of the project compared gene expression profiles from injured rat retina [Geisert et al., IOVS 2003 44: E–Abstract 2967], brain [Matzilevich et al., J Neurosci Res 2002 67:646] and spinal cord [Di Giovanni et al., Ann Neurol 2003 53:45]. Gene expression profiles at 4 and 24 hours after injury were analyzed using the Affymetrix Rat Chip (RG_U34A). These data were then compared to a data set [www.webqtl.org] in which the genes were used to map quantitative traits loci (QTLs) for the mouse forebrain. Results: We show that the healing responses of the retina, brain and spinal cord shared a set of immediate early genes, including the transcription factors Fos, Fosl1 (Fra–1), Cebpd, Egr1 (Krox–24), and Nr4a1 (NGFI–B). Using QTL analysis, we also show that these immediate early genes mapped to chromosome 4, at 110–120 Mb in the mouse. Conclusions:The results from the present study suggest that the response to injury in the CNS may be controlled, in part, by common regulatory mechanisms.
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