September 2016

Volume 57, Issue 12

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OPEN ACCESS
ARVO Annual Meeting Abstract  |   September 2016
NMDA-induced Retinal Excitotoxicity Triggers Inflammation and Inflammasome
Activation in Mice.
Pavlina Tsoka; Keiko Kataoka; Joan W Miller; Demetrios G. Vavvas
 Author Affiliations & Notes
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 2248. doi:

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Abstract

Purpose : Overactivation of the N-methyl-D-aspartate (NMDA) receptor results in

excitotoxic cell death and has been implicated in various eye disorders. However,
the death modality and the inflammatory response following NMDA-induced retinal
injury have not been fully characterized. Our purpose was to investigate the time
course of cell death, the inflammatory response and the role of the NLRP3
inflammasome in experimental NMDA-induced retinal excitotoxicity.
Methods : NMDA-induced retinal excitotoxicity was induced in C57BL/6 mice by an
intravitreal injection of 2 ul of NMDA (100nmoles), while the control group received
an intravitreal injection of 2 ul of vehicle only (PBS). A time course of retinal cell
death was assessed by TUNEL assay. The inflammatory process following NMDA-
induced retinal injury was evaluated by macrophage/microglia infiltration and
inflammatory cytokines secretion by immunohistochemistry and RT-PCR
respectively. Induction of NLRP3 inflammasome by NMDA excitotoxicity in the
retina was assessed by RT-PCR and ELISA. Finally, the neuroprotective role of
inflammasome inhibition in NMDA-induced retinal excitotoxicity was investigated in
NLRP3 and caspase-1/11 KO mice.

Results : NMDA intravitreal administration resulted in rapid cell death of several

types of retinal neurons, starting 4 hours post injury with cells in the inner nuclear
layer (INL) and followed 12 hours post injury with retinal ganglion cell layer and
photoreceptors. Cell death peaked 24 hours post injection for all retina layers.
Monocyte chemoattractant protein 1, macrophage/microglia infiltration and
Interleukin-1β secretion peaked 24 hours post injury, while NLRP3 and caspase-1
levels peaked 7 days post injury. Furthermore, cell death in the INL was significantly
reduced in caspase 1/11 KO and NLRP3 KO mice.

Conclusions : Conclusions: This study contributes to the understanding of the

NMDA-induced excitotoxicity in the retina and highlights the role of inflammatory
response following this type of injury. In addition it suggests potential therapeutic
targets for diseases where excitotoxicity by the NMDA receptor is involved.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in
Seattle, Wash., May 1-5, 2016.