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Wennan Lu, Keith Campagno, Farraj Albalawi, Claire H Mitchell; IL-1β is released by retinal microglial cells in response to ATP and can damage retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3729.
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© ARVO (1962-2015); The Authors (2016-present)
Elevated intraocular pressure (IOP) leads to increased inflammatory signals in the retina and damage to the retinal ganglion cells (RGCs), but the mechanisms linking these events are unclear. We have previously shown that increased IOP leads to a mechanosensitive release of ATP from optic nerve head astrocytes, and that stimulation of P2X7 receptors for ATP is associated with increased levels of cytokine IL-1β in the retina. Here we ask whether microglial cells release IL-1β in response to ATP and whether IL-1β damages RGCs.
Isolated retinal microglia cells were primed for 3 hrs with LPS and stimulated with ATP. IL-1β was determined with an ELISA. The photopic negative response (PhNR) was recorded using a Celaris ERG system in BALB/c mice. RGCs were isolated using the immunopanned procedure and stained with a MAP2 antibody.
The release of IL-1β from isolated retinal microglial cells was increased over 8 fold after exposure of cells to ATP. To understand the impact of IL-1β on retinal function, recombinant mouse IL-1β (20 ng/ml) was injected intravitreally, with saline in the contralateral eye. The PhNR was assessed using ERG before injection and 3 days after injection. Eyes receiving an injection of IL-1β showed a reduction in PhNRs at 3 days. Preliminary results suggest the a-wave and b-wave were unaffected, consistent with a decrease in inner retina/RGC function. Isolated immunopanned RGCs displayed elaborate neurite growth stained with MAP2. Addition of 10 ng/ml IL-1β on day 1 reduced the growth of neurites, and reduced surviving RGC numbers.
The ability of IL-1β to reduce the PhNR in vivo and damage RGCs in vitro suggest the cytokine is toxic to RGCs. The ability of retinal microglial cells to release IL-1β in response to ATP is relevant to the rise in extracellular ATP found with elevated IOP. Whether ATP released by IOP elevation can trigger IL-1β release from microglial cells and whether this in turn damages RGCs in vivo remains to be determined.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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