September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
S100 alone and in combination with HSP27 leads to specific retinal ganglion cell loss in an IOP-independent glaucoma model
Author Affiliations & Notes
  • Stephanie C Joachim
    Ophthalmology, Ruhr-University Bochum, Bochum, Germany
  • Christina Casola
    Ophthalmology, Ruhr-University Bochum, Bochum, Germany
  • Sabrina Reinehr
    Ophthalmology, Ruhr-University Bochum, Bochum, Germany
  • Sandra Kuehn
    Ophthalmology, Ruhr-University Bochum, Bochum, Germany
  • H Burkhard Dick
    Ophthalmology, Ruhr-University Bochum, Bochum, Germany
  • Footnotes
    Commercial Relationships   Stephanie Joachim, None; Christina Casola, None; Sabrina Reinehr, None; Sandra Kuehn, None; H Burkhard Dick, None
  • Footnotes
    Support  German Research Foundation (grant JO-886/1-3)
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 488. doi:
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      Stephanie C Joachim, Christina Casola, Sabrina Reinehr, Sandra Kuehn, H Burkhard Dick; S100 alone and in combination with HSP27 leads to specific retinal ganglion cell loss in an IOP-independent glaucoma model. Invest. Ophthalmol. Vis. Sci. 2016;57(12):488.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : As previously shown, immunization with ocular antigens, like heat shock protein 27 (HSP27), leads to RGC loss in an autoimmune glaucoma model. Aim of this study was to investigate how immunization with S100 alone and in combination with HSP27 affects neuronal and glial cells in the retina at late stages.

Methods : Rats were immunized with S100 or S100 plus HSP27 (COMB) and compared to controls (n=5/group). 4 weeks after immunization retinas were processed for immunehistology and Western blot analysis. Retinal ganglion cells (Brn-3a), amacrine cells (ChAT), and photoreceptors (rhodopsin, opsin) were quantified. Additionally, Macroglia (GFAP, Vimentin) and microglia (Iba1, ED1) were analyzed. Groups were compared via ANOVA with Dunnett’s post-hoc test.

Results : No IOP alterations were noted in both immunized groups throughout the study (S100/COMB p>0.05). About a 30% RGC loss was observed in both immunized groups at 4 weeks (S100 p=0.005; COMB p=0.004). Cholinergic amacrine cells were also affected (S100 p=0.02; COMB p=0.05), while cone (S100 p=0.5; COMB p=0.2) and rod photoreceptors (S100 p=0.9; COMB p=0.1) remained intact in both immunized groups. Fewer Iba1+ microglia cells were noted in the immunized groups at this late point in time (S100/COMB p=0.0001), especially in the RGC layer. Otherwise, the number of activated microglia was comparable in all groups (S100/COMB p>0.1). A slight increase in astrocyte reactivity was noted in both immunized groups (S100 p=0.05; COMB p=0.04), while Müller glia remained unaltered (S100/COMB p=0.9).

Conclusions : Findings from this study indicate that immunization with ocular antigens rather damages RGCs and amacrine cells than photoreceptors. Interestingly, the microglia population decreased in these degenerated retinas. Either the microglia response was shifted to another place with an acute degeneration, perhaps the optic nerve, or the immune reaction led to an attack against microglia at this advanced point in time. Hence, this IOP-independent glaucoma model can serve as a tool to study specific neuroprotective agents.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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