PLoS ONE (Jan 2012)

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
https://doi.org/10.1371/journal.pone.0040616
Journal volume & issue
Vol. 7, no. 7
p. e40616

Abstract

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BackgroundAntibodies 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.Methodology/principal findingsRats 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.Conclusions/significanceOur 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.