Heat Shock Protein Upregulation Supplemental to Complex mRNA Alterations in Autoimmune Glaucoma

Abstract

Glaucomatous optic neuropathy is a common cause for blindness. An elevated intraocular pressure is the main risk factor, but also a contribution of the immune system seems likely. In the experimental autoimmune glaucoma model used here, systemic immunization with an optic nerve homogenate antigen (ONA) leads to retinal ganglion cell (RGC) and optic nerve degeneration. We processed retinae for quantitative real-time PCR and immunohistology 28 days after immunization. Furthermore, we performed mRNA profiling in this model for the first time. We detected a significant RGC loss in the ONA retinae. This was accompanied by an upregulation of mRNA expression of genes belonging to the heat shock protein family. Furthermore, mRNA expression levels of the genes of the immune system, such as C1qa, C1qb, Il18, and Nfkb1, were upregulated in ONA animals. After laser microdissection, inner retinal layers were used for mRNA microarrays. Nine of these probes were significantly upregulated in ONA animals (p < 0.05), including Hba-a1 and Cxcl10, while fifteen probes were significantly downregulated in ONA animals (p < 0.05), such as Gdf15 and Wwox. Taken together, these findings provide further insights into the pivotal role of the immune response in glaucomatous optic neuropathy and could help to identify novel diagnostic or therapeutic strategies.

A Systematic Review of the Neuroprotective Role and Biomarker Potential of GDF15 in Neurodegeneration

“…In contrast, no change was observed at any timepoint in the mouse retina following light-induced retinal degeneration or in experimentally induced uveitis (Ban et al, 2017). Moreover, 28 days after systemic injection of optic nerve homogenate antigen, mRNA expression of this cytokine was diminished in the inner retinal layer (Reinehr et al, 2022). Therefore, while GDF15's association with retinal degeneration varies, fully understanding its role in neuroretina inflammation requires further evidence and additional timepoints.…”