S100 Alone Has the Same Destructive Effect on Retinal Ganglion Cells as in Combination with HSP 27 in an Autoimmune Glaucoma Model

Abstract

As previously shown, immunization with ocular antigens, like heat shock protein 27 (HSP 27), leads to retinal ganglion cell loss in an autoimmune glaucoma model. Aim of this study was to assess how immunization with S100 alone and in combination with HSP 27 affects retinal ganglion and macroglia cells. Rats were immunized with S100 or S100 plus HSP 27 (COMB). Neuronal cell density was evaluated on Nissl-stained flatmounts. Immunized groups showed a significant neuronal cell loss (S100, p = 0.005; COMB, p = 0.0005). A significant loss of retinal ganglion cells was also observed in both immunized groups on Brn-3a stained retinal cross-sections (S100, p = 0.003; COMB, p = 0.001). An increase in GFAP(+) area was noted in both groups (S100, p = 0.01; COMB, p = 0.001). In contrary, vimentin staining was not altered (S100/COMB, p > 0.05). In summary, immunization with solely S100 leads to retinal ganglion cell damage and reactive gliosis. While the combination of S100 plus HSP 27 also caused retinal ganglion cell loss and a glia response, the combination of the two antigens did not cause additional damage or more severe cell loss. We assume that both antigens might interact, possibly having inhibitory effects on each other and thus preventing additional damage to the retina.

Early remodelling of the extracellular matrix proteins tenascin‐C and phosphacan in retina and optic nerve of an experimental autoimmune glaucoma model

“…Although only few changes in the mRNA expression of GFAP were noted in this study after 14 days. Previous results of our group revealed a reactive gliosis at later points in time [4]. Here, phosphacan expression in Müller glia occurs earlier following retinal and optic nerve damage than gliosis in this model.…”

“…In this study, we analyzed the expression pattern of the ECM glycoprotein tenascin-C and the CSPG phosphacan/RPTPb/f in an IOPindependent EAG model. Data from previous studies showed a loss of RGCs in the ONA as well as in the S100 group 28 days after immunization [4,5]. Here, we investigated possible ECM alterations in this model at earlier points in time.…”

“…Increased autoantibody levels against S100 were detected in patients with glaucoma [3]. The immunization with ONA and S100 leads to a loss of RGCs and to optic nerve damage, without IOP elevation, starting at about day 28 after immunization [2,4,5]. Also, autoreactive antibodies were found in the retina and the optic nerve of immunized animals as well as signs of reactive gliosis and apoptosis [6].…”

Specific Inner Retinal Layer Cell Damage in an Autoimmune Glaucoma Model Is Induced by GDNF With or Without HSP27

“…In previous studies, immunization with HSP27, a purified antigen, led to loss of RGCs. 15,16 In addition to autoantibodies to HSP27, elevated antibodies against the glial cell line-derived neurotrophic factor (GDNF) were found in glaucoma patients with normal tension. It is still unclear if the antibodies found in glaucoma patients are the cause or the consequence of the disease.…”

Derzeitiger Stand zur primären Neuroprotektion beim Glaukom

“…Um den Zusammenhang zwischen einer Dysregulation des Immunsystems und dem Glaukom besser untersuchen zu können, wurde das Experimentelle Autoimmune Glaukommodell (EAG-Modell) entwickelt. In diesem Modell kommt es, unabhängig vom IOD, nach 28 Tagen zu einem Verlust von RGZ und einer Degeneration der Sehnerven [21,22]. Durch die Immunisierung mit okulären Antigenen, wie z.…”