Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.
Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.
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DOI:
10.1371/journal.pone.0040616
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Grus FH
中科院分区:
文献类型:
--
作者:
Joachim SC;Gramlich OW;Laspas P;Schmid H;Beck S;von Pein HD;Dick HB;Pfeiffer N;Grus FH
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.
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