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

  • \(\textit {Background}\): 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. \(\textit {Methodology/Principal Findings}\): 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\(\pm\)41.9; CO: 137.6\(\pm\)36.8, p = 0.0006; \(%GFAP^{+}\) area: RGA: 8.5\(\pm\)3.4; CO: 5.9\(\pm\)3.6, p = 0.006) as well as elevated level of \(Iba1^{+}\) microglia cells (p = 0.003) was observed in retinas of RGA animals. \(\textit {Conclusions/Significance}\): 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.

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Metadaten
Author:Stephanie Christine JoachimORCiDGND, Oliver W. GramlichGND, Panagiotis LaspasGND, Heiko SchmidGND, Sabine BeckGND, Harald D. von PeinGND, Burkhard DickORCiDGND, Norbert PfeifferGND, Franz-Hermann GrusGND
URN:urn:nbn:de:hbz:294-72063
DOI:https://doi.org/10.1371/journal.pone.0040616
Parent Title (English):PLoS one
Publisher:Public Library of Science
Place of publication:San Francisco
Document Type:Article
Language:English
Date of Publication (online):2020/06/04
Date of first Publication:2012/07/26
Publishing Institution:Ruhr-Universität Bochum, Universitätsbibliothek
Tag:Antibodies; Glaucoma; Hematoxylin staining; Immunohistochemistry techniques; Microglial cells; Optic nerve; Retina; Retinal ganglion cells
Volume:7
Issue:7, Artikel e40616
First Page:e40616-1
Last Page:e40616-13
Institutes/Facilities:Knappschaftskrankenhaus Bochum, Klinik für Augenheilkunde
open_access (DINI-Set):open_access
Licence (English):License LogoCreative Commons - CC BY 4.0 - Attribution 4.0 International