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Juan Qu, Tatjana Jakobs; The Time Course of Gene Expression during Reactive Gliosis in the Optic Nerve. Invest. Ophthalmol. Vis. Sci. 2013;54(15):5586.
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© ARVO (1962-2015); The Authors (2016-present)
The “reactivity” of astrocytes is a complex process that involves changes in gene expression and morphological remodeling. The mouse optic nerve head has a focal concentration of astrocytes ensheathing the unmyelinated axons of retinal ganglion cells and is a favorable model for studying astrocyte structure and function. Here, we investigated the time course of gene expression changes during reactive gliosis.
We triggered gliosis at the optic nerve head by retro orbital nerve crush, without direct injury to the glia. We followed the expression profiles of 14,000 genes from 1 day to 3 months, as a glial scar formed in the optic nerve. Microarray data were confirmed using qRT-PCR, single-cell RT-PCR and immunohistochemistry.
The transcriptome showed profound changes. The numbers of differentially regulated genes were greatest shortly after injury. They then dropped, returning nearly to resting levels by 3 months. Different genes were modulated with very different time courses, and functionally distinct groups of genes responded in partially overlapping waves. These corresponded roughly to two quick waves of inflammation and cell proliferation, a slow wave of tissue remodeling and debris removal, and a final stationary phase that primarily reflects permanent structural changes in the axons. Responses from astrocytes, microglia and oligodendrocytes were distinctively different, both molecularly and morphologically. Comparisons to other models of brain injury and to glaucoma indicated that the glial responses depended on both the tissue and the injury.
Our results revealed both acute and chronic time-dependent molecular events during glial scar formation. Attempts to modulate glial function after axonal injuries should consider different mechanistic targets at different times following the insult.
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