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Editors Selection IGR 15-2

Experimental Glaucoma: Immunological mechanisms

Comment by Gülgün Tezel on:

53440 Innate immune network in the retina activated by optic nerve crush, Templeton JP; Freeman NE; Nickerson JM et al., Investigative Ophthalmology and Visual Science, 2013; 54: 2599-2606

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Innate immunity has been suggested to play a role in ocular neurodegenerative diseases, including glaucoma and aging-related macular degeneration. Templeton et al. employed transcriptome profiling to investigate the network of genes associated with the innate immunity in the mouse retina. Analysis of the gene expression datasets indicated that various components of the innate immune system are expressed by retinal cells, and a co-regulated group of transcripts form a network in the normal retina. By examining the changes in retinal gene expression, the authors also defined that the retina-intrinsic set of transcripts linked to the innate immunity is up-regulated two days after optic nerve crush. The activated genes included various components of the complement cascade and cellular markers of glial cells, including astrocytes, Müller cells, microglia. In addition, the authors examined the innate immune network in the DBA/2J mouse with hereditary glaucoma. Parallel to previous findings of gene or protein expression studies of human glaucoma and animal models, the database analysis indicated that a similar set of genes create the core of innate immune responses to glaucoma and optic nerve crush. As the authors pointed out, many of the identified genes also included those previously linked to agingrelated macular degeneration. Thus, based on the gene expression profiles, different types of insults to the retina seem to activate a similar innate immune network and the complement cascade forms part of this molecular response system.

While the authors used an elegant approach to generate the network maps from large datasets, the need grows to translate the gene expression datasets into functional information.

It is so appealing to speculate that, besides reflecting the molecular response to retinal stress or injury, many of the activated genes may be risk factors for retinal disease. As evident by strong association of many allelic variants of the complement components to aging-related macular degeneration, the innate immune network can become dysregulated when its members carry mutations. Epigenetic or post-translational alterations may similarly shift the molecular regulation of immune responses towards neurodegenerative inflammation. While the authors used an elegant approach to generate the network maps from large datasets, the need grows to translate the gene expression datasets into functional information.

If the pathogenic importance of innate immune activity or dysregulation is verified, then specific components in the innate immune network or specific cell types expressing the major components of the network can be therapeutically targeted to restore immune homeostasis and enhance neuronal survival in glaucoma and other neurodegenerative diseases.

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