Abstract
Purpose:
In glaucoma, inflammation contributes to the disease progression; as a direct contributor to the pathology or a result of the degeneration. In-depth knowledge is needed on the mechanisms by which inflammation contributes to retinal ganglion cell (RGC) death, before an efficient anti-inflammatory treatment may be proposed. Therefore, we here studied whether and how RGCs are affected by a severe LPS-induced retinal inflammation.
Methods:
Inflammation was induced by administration of bacterial lipopolysaccharide (LPS) to organotypic cultured mouse retina. At 24 h, 48 h and 5 days after LPS- administration these parameters were studied: i) microglial activation using Iba-1, ED1- and galectin-3 immunohistochemistry (IHC), ii) cytokine release profile, iii) gliosis (GFAP-IHC), iv) gross morphology and v) apoptosis and RGC (NeuN-IHC) death in the ganglion cell layer (gcl). Non-LPS exposed retina was used as control.
Results:
We demonstrate a LPS-induced retinal inflammation model, characterized by a severe inflammatory response, exemplified by a significant increase in: 1) microglia proliferation, 2) numbers of activated cell profiles, 3) expression of markers for a late and severe inflammatory response (i.e. ED1, galectin-3) and 4) inflammatory cytokines. TNF-α, IL-2, IL-6 and, especially the cytokine KC/GRO, was found in high levels. In addition, tissue damage after LPS exposure was further demonstrated by a glia response. An increase in apoptotic cells in the gcl was found, but not a loss in RGCs.
Conclusions:
There is an urgent need for neuroprotective treatments for neurodegenerations, including glaucoma. Knowledge on key events in the inflammatory process described to accompany many neurodegeneration, may lead to proposals of novel treatment paradigms. Using the present LPS-induced inflammation protocol, a significant inflammatory response was demonstrated, proven by the expression of ED1 and galectin-3. However, although an increase in apoptotic cells in the gcl was found, it was not followed by a loss of cells in the GCL, including RGC, in the time-interval studied. This may be explained by the high expression of the cytokine KC/GRO, reported to have a neuroprotective effect in other neurodegenerative diseases. Further studies on KC/GRO's role inflammation is needed for exploring its potential as a neuroprotective candidate.