Retinal and Optic Nerve Damage is Associated with Early Glial Responses in an Experimental Autoimmune Glaucoma Model

Abstract

It is well established that the immunization with ocular antigens causes a retinal ganglion cell (RGC) decline, which is accompanied by glia alterations. In this study, the degenerative effects of the immunization with an optic nerve homogenate (ONA) and its purified compound S100 were analyzed on retinas and optic nerves. Since a participation of glia cells in cell death mechanisms is currently discussed, rats were immunized with S100 or ONA. At 14 and 28 days, immune-histological and Western blot analyses were performed to investigate the optic nerve structure (SMI-32), retinal ganglion cells (Brn-3a), apoptosis (cleaved caspase 3, FasL), and glial profile (Iba1, ED1, GFAP, vimentin). Neurofilament dissolution in S100 animals was evident at 14 days (p = 0.047) and increased at 28 days (p = 0.01). ONA optic nerves remained intact at early stages and degenerated later on (p = 0.002). In both groups, RGC loss was detected via immune-histology and Western blot at 28 days (ONA: p = 0.02; S100: p = 0.005). Additionally, more Iba1(+) retinal microglia could be detected at early stages (ONA: p = 0.006; S100: p = 0.028). A slight astrocyte response was detected on Western blots only on ONA retinas (p = 0.01). Hence, the RGC and optic nerve decline was partly antigen dependent, while neuronal loss is paralleled by an early microglial response.

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

“…In previous studies of our group we could demonstrate that apoptotic processes occur in the retina as early as 14-22 days after ONA immunization [6], which might induce tenascin-C remodelling. Also, optic nerve degeneration was noted in the EAG model at days 14 and 28 [34,72]. Other studies have already demonstrated that tenascin-C expression is highly associated with glial scar formation.…”

Autoimmune aspects in glaucoma

“…The optic disc appeared without pathological findings in all animals up to 6 weeks after immunization but importantly, we observed a significant demyelination of the optic nerve and reactive gliosis, which often accompanied the IgG accumulations or appeared in co-localization with IgG-deposition and fragmented nuclei (Fig. 5 E) (Joachim et al, 2012;Noristani et al, 2016).…”

“…Further studies from Joachim et al also demonstrated strong microglial involvement and hints for the caspase-3 mediated apoptosis pathway in the EAG model without any elevation of intraocular pressure (Joachim et al, 2012(Joachim et al, , 2014Noristani et al, 2016). Retinal IgG accumulations were often accompanied in co- Retinal sections were immunostained for IgG accumulations and counterstained with haematoxylin.…”

“…©PLOSone. (Joachim et al, 2014;Noristani et al, 2016). Caspase-3 is a key mediator of apoptosis and activates caspase-activated DNase which is able to enter the nucleus and cleaves DNA in fragments typical for apoptotic cells (Janeway et al, 2002).…”

Biomarkers for glaucoma: from the lab to the clinic

“…37 Moreover, RGC loss after immunization with retinal antigens is accompanied by antibody depositions and increased levels of microglia. [38][39][40]…”