June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
The Time Course of Gene Expression during Reactive Gliosis in the Optic Nerve
Author Affiliations & Notes
  • Juan Qu
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Tatjana Jakobs
    Ophthalmology, Massachusetts Eye & Ear Infirmary, Boston, MA
  • Footnotes
    Commercial Relationships Juan Qu, None; Tatjana Jakobs, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 5586. doi:
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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)

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Abstract
 
Purpose
 

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.

 
Methods
 

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.

 
Results
 

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.

 
Conclusions
 

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.

 
 
Clustering analysis of the optic nerve head samples and the genes differentially expressed after crush. Each column is one array sample. Each row is one gene probe set that had been normalized to have mean 0 and standard deviation 1. The crushed samples (filled color squares above the heatmap) from each time point formed unique subgroups before merging into one big cluster, which was distinctly different from the cluster of the naïve and the contralateral controls (open squares). The genes thus changed expression levels in a time dependent manner.
 
Clustering analysis of the optic nerve head samples and the genes differentially expressed after crush. Each column is one array sample. Each row is one gene probe set that had been normalized to have mean 0 and standard deviation 1. The crushed samples (filled color squares above the heatmap) from each time point formed unique subgroups before merging into one big cluster, which was distinctly different from the cluster of the naïve and the contralateral controls (open squares). The genes thus changed expression levels in a time dependent manner.
 
Keywords: 429 astrocyte • 577 lamina cribrosa • 535 gene microarray  
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