Suppression of SNARE‐dependent exocytosis in retinal glial cells and its effect on ischemia‐induced neurodegeneration

Abstract

Nervous tissue is characterized by a tight structural association between glial cells and neurons. It is well known that glial cells support neuronal functions, but their role under pathologic conditions is less well understood. Here, we addressed this question in vivo using an experimental model of retinal ischemia and transgenic mice for glia‐specific inhibition of soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE)‐dependent exocytosis. Transgene expression reduced glutamate, but not ATP release from single Müller cells, impaired glial volume regulation under normal conditions and reduced neuronal dysfunction and death in the inner retina during the early stages of ischemia. Our study reveals that the SNARE‐dependent exocytosis in glial cells contributes to neurotoxicity during ischemia in vivo and suggests glial exocytosis as a target for therapeutic approaches.

Age‐Related Macular Degeneration: New Paradigms for Treatment and Management of AMD

“…In both cases, the ATP release from Müller glia is a Ca 2+ -independent process. This was supported by experimental data which suggest that ATP is released from Müller cells in a SNARE-independent manner, probably via hemichannels [ 90 – 94 ].…”

Cell-Type-Specific Complement Expression in the Healthy and Diseased Retina

“…Retinal tissue injury is a common manifestation of retinal disease. To evaluate how tissue injury might change cell-type-specific complement expression, we used a retinal ischemia/reperfusion (I/R) injury model to induce acute retinal degeneration (Wagner et al, 2017). We found a significant increase in the expression of complement activators 24 h post-ischemia in the different isolated cell populations (Figure 7).…”

Astrocytic signaling supports hippocampal–prefrontal theta synchronization and cognitive function

“…In spite of being used in different labs in the past decade (Oliveira et al, 2015), the validity of this mouse model was challenged (Fujita et al, 2014). Nevertheless, we and others have recently validated this model for the study of signaling dependent on astrocyte exocytosis (Pankratov & Lalo, 2015;Sultan et al, 2015;Wagner et al, 2017). In our lab, we firstly performed complementary sets of experiments to validate the co-expression of dnSNARE and reporter transgenes, the inducible control, the astrocyte specificity and the level of transgene expression among brain regions and subjects.…”