Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation

Oliver W Gramlich; Cheyanne R Godwin; David Wadkins; Benjamin W Elwood; Markus H Kuehn

doi:10.3390/ijms22147581

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Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation

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Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation

Oliver W Gramlich, Cheyanne R Godwin, David Wadkins, Benjamin W Elwood and Markus H Kuehn

International journal of molecular sciences, Vol.22(14), p.7581

07/15/2021

DOI: 10.3390/ijms22147581

PMCID: PMC8306430

PMID: 34299211

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Abstract

Glaucoma is a leading cause of irreversible blindness worldwide, and increased intraocular pressure (IOP) is a major risk factor. We aimed to determine if early functional and molecular differences in the glaucomatous retina manifest before significant retinal ganglion cell (RGC) loss is apparent. Adenoviral vectors expressing a pathogenic form of myocilin (Ad5.MYOC) were used to induce IOP elevation in C57BL/6 mice. IOP and pattern electroretinograms (pERG) were recorded, and retinas were prepared for RNA sequencing, immunohistochemistry, or to determine RGC loss. Ocular injection of Ad5.MYOC leads to reliable IOP elevation, resulting in significant loss of RGC after nine weeks. A significant decrease in the pERG amplitude was evident in eyes three weeks after IOP elevation. Retinal gene expression analysis revealed increased expression for 291 genes related to complement cascade, inflammation, and antigen presentation in hypertensive eyes. Decreased expression was found for 378 genes associated with the γ-aminobutyric acid (GABA)ergic and glutamatergic systems and axon guidance. These data suggest that early functional changes in RGC might be due to reduced GABA A receptor signaling and neuroinflammation that precedes RGC loss in this glaucoma model. These initial changes may offer new targets for early detection of glaucoma and the development of new interventions.

myocilin

γ-aminobutyric acid (GABA)

retinal ganglion cell loss

neuroinflammation

glaucoma

pattern electroretinography

Details

Title: Subtitle: Early Functional Impairment in Experimental Glaucoma Is Accompanied by Disruption of the GABAergic System and Inceptive Neuroinflammation
Creators: Oliver W Gramlich - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA 52242, USA
Cheyanne R Godwin - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA 52242, USA
David Wadkins - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA 52242, USA
Benjamin W Elwood - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA 52242, USA
Markus H Kuehn - Department of Ophthalmology and Visual Sciences, The University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: International journal of molecular sciences, Vol.22(14), p.7581
DOI: 10.3390/ijms22147581
PMID: 34299211
PMCID: PMC8306430
NLM abbreviation: Int J Mol Sci
ISSN: 1661-6596
eISSN: 1422-0067
Publisher: MDPI
Language: English
Date published: 07/15/2021
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
Record Identifier: 9984112433302771

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