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Leo Volkov, Lilliana Suarez, Levi Todd, Andrew J Fischer; Reactive Microglia are Neuroprotective in the Mammalian Retina. Invest. Ophthalmol. Vis. Sci. 2016;57(12):4505.
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© ARVO (1962-2015); The Authors (2016-present)
Microglia are known to become reactive in response to cell damage and death in the retina during the progression of disease. Depending on the context, reactive microglia can provide neuroprotection or exacerbate neuronal damage. We investigate how reactive microglia might influence neuronal survival in the retinas of adult mice.
All experiments utilized male and female C57BL/6J postnatal mice (100-120 days old). Compounds were delivered via intraocular injections. One eye received the “treatment" and the contralateral eye served as the "control". Compounds included sterile saline, recombinant mouse IL-1β to induce microglial reactivity, and clodronate liposomes to selectively ablate microglia. Retinas were damaged by a single injection of N-Methyl-D-aspartate (NMDA). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to detect dying cells. Long-term neuronal survival was assessed by immunolabeling of calretinin, HuD, and Brn3a. Following treatment paradigms, retinas were harvested and processed for indirect immunofluorescence, digital photomicroscopy, or qRT-PCR. Significance of difference (*p<0.05; n≥5) was determined by using a paired, two-tailed t-test.
We find that intraocular injections of IL-1β stimulate microglia to become reactive, proliferate, acquire an ameboid morphology, and up-regulate F4/80. IL-1β-treated microglia provide neuroprotection, as evident by a reduction in TUNEL+ cells and an increase in calretinin+ amacrine cells and Brn3a+ cells in the ganglion cell layer. Following ablation of microglia, we found significant increases in numbers of dying cells, and significant decreases in numbers of surviving neurons.
Our data indicate that IL-1β-primed microglia can provide neuroprotection in acutely damaged mammalian retina. Subsequently, the absence of reactive microglia exacerbates neuronal cell death in the retina.
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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