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izhar Livne-bar, John G Flanagan, Karsten Gronert, Jeremy M Sivak; The Lipoxin LXB4 Reduces Mitochondrial Oxidative Stress in Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2019;60(9):620.
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© ARVO (1962-2015); The Authors (2016-present)
The small lipid mediators LXA4 and LXB4 promote retinal ganglion cells (RGC) survival following acute metabolic stress and sustained IOP insult. However, the mechanism underlying this effect is still unclear. We report here that LXB4 treatment can reduce markers of mitochondrial oxidative stress in RGCs following acute metabolic and oxidative injury in vivo, and in neuronal cultures.
Retinal acute metabolic stress was generated by intravitreal injections of Kainic acid (KA). RGC survival was quantified using specific antibodies. Inner retinal mitochondrial oxidative stress was assessed by measuring superoxide dismutase 2 (SOD2) induction. Oxidative stress in neuronal cell culture was induced by Paraquat and cell survival quantified by XTT assay. In parallel, mitochondrial oxidative stress in these cultures was assessed using Mitosox assay.
We show that intravitreal LXB4 treatment strongly increases RGC survival following metabolic injury by 99.3%. In addition, this LXB4 treatment reduces RGC mitochondrial stress, as indicated by significantly reduced SOD2 levels (59.9%). Similarly, direct LXB4 treatment of cultured neurons increases survival from oxidative-stress insult by 56.2%, and reduces the mitochondrial oxidative stress signal by 75%.
These results suggest that the retinal protective effect of the lipoxin LXB4 is mediated, at least in part, by reducing mitochondrial oxidative stress. We are currently investigating the signaling pathway mediating the LXB4 effect on mitochondrial stress responses, and are assessing whether LXB4 promotes a similar mitochondrial resilience in a chronic, IOP-induced injury model.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.
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