Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens

Stephanie C Joachim; Oliver W Gramlich; Panagiotis Laspas; Heiko Schmid; Sabine Beck; Harald D von Pein; H Burkhard Dick; Norbert Pfeiffer; Franz H Grus

doi:10.1371/journal.pone.0040616

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Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens

Journal article

Open access

Peer reviewed

Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens

Stephanie C Joachim, Oliver W Gramlich, Panagiotis Laspas, Heiko Schmid, Sabine Beck, Harald D von Pein, H Burkhard Dick, Norbert Pfeiffer and Franz H Grus

PloS one, Vol.7(7), pp.e40616-e40616

2012

DOI: 10.1371/journal.pone.0040616

PMCID: PMC3406064

PMID: 22848388

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Abstract

Antibodies against retinal and optic nerve antigens are detectable in glaucoma patients. Recent studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immun-mediated retinal ganglion cell loss in rats. Rats immunized with a retinal ganglion cell layer homogenate (RGA) had a reduced retinal ganglion cell density on retinal flatmounts (p = 0.007) and a lower number of Brn3(+) retinal ganglion cells (p = 0.0001) after six weeks. The autoreactive antibody development against retina and optic nerve was examined throughout the study. The levels of autoreactive antibodies continuously increased up to 6 weeks (retina: p = 0.004; optic nerve: p = 0.000003). Additionally, antibody deposits were detected in the retina (p = 0.02). After 6 weeks a reactive gliosis (GFAP density: RGA: 174.7±41.9; CO: 137.6±36.8, p = 0.0006; %GFAP(+) area: RGA: 8.5±3.4; CO: 5.9±3.6, p = 0.006) as well as elevated level of Iba1(+) microglia cells (p = 0.003) was observed in retinas of RGA animals. Our findings suggest that these antibodies play a substantial role in mechanisms leading to retinal ganglion cell death. This seems to lead to glia cell activation as well as the invasion of microglia, which might be associated with debris clearance.

Autoantigens - pharmacology

Immunization

Cell Death - immunology

Rats, Inbred Lew

Rats

Retinal Ganglion Cells - immunology

Male

Retinal Ganglion Cells - pathology

Autoantibodies - immunology

Animals

Microglia - immunology

Autoantigens - immunology

Glaucoma - immunology

Microglia - pathology

Glaucoma - pathology

Cell Death - drug effects

Details

Title: Subtitle: Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens
Creators: Stephanie C Joachim - Experimental Eye Research Institute, Ruhr University Eye Hospital, Bochum, Germany. stephanie.joachim@rub.de
Oliver W Gramlich
Panagiotis Laspas
Heiko Schmid
Sabine Beck
Harald D von Pein
H Burkhard Dick
Norbert Pfeiffer
Franz H Grus
Resource Type: Journal article
Publication Details: PloS one, Vol.7(7), pp.e40616-e40616
DOI: 10.1371/journal.pone.0040616
PMID: 22848388
PMCID: PMC3406064
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Language: English
Date published: 2012
Academic Unit: Iowa Neuroscience Institute; Neuroscience and Pharmacology; Ophthalmology and Visual Sciences
Record Identifier: 9984070725002771

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