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Panton-Valentine Leucocidin of Staphylococcus aureus Induces Oxidative Stress and Neurotransmitter Imbalance in a Retinal Explant Model.

Abstract：

Purpose:Endophthalmitis models have reported the virulent role of Panton-Valentine leucocidin (PVL) secreted by Staphylococcus aureus on the retina. PVL targets retinal ganglion cells (RGCs), expressing PVL membrane receptor C5aR. Interactions between PVL and retinal cells lead to glial activation, retinal inflammation, and apoptosis. In this study, we explored oxidative stress and retinal neurotransmitters in a rabbit retinal explant model incubated with PVL. Methods:Reactive oxygen species (ROS) production in RGCs has been assessed with fluorescent probes and immunohistochemistry. Nuclear magnetic resonance (NMR) spectroscopy quantified retinal concentrations of antioxidant molecules and neurotransmitters, and concentrations of neurotransmitters released in the culture medium. Quantifying the expression of some pro-inflammatory and anti-inflammatory factors was performed using RT-qPCR. Results:PVL induced a mitochondrial ROS production in RGCs after four hours' incubation with the toxin. Enzymatic sources of ROS, involving nicotinamide adenine dinucleotide phosphate-oxidase and xanthine oxidase, were also activated after four hours in PVL-treated retinal explants. Retinal antioxidants defenses, that is, glutathione, ascorbate and taurine, decreased after two hours' incubation with PVL. Glutamate retinal concentrations and glutamate release in the culture medium remained unaltered in PVL-treated retinas. GABA, glycine, and acetylcholine (Ach) retinal concentrations decreased after PVL treatment. Glycine release in the culture medium decreased, whereas Ach release increased after PVL treatment. Expression of proinflammatory and anti-inflammatory cytokines remained unchanged in PVL-treated explants. Conclusions:PVL activates oxidative pathways and alters neurotransmitter retinal concentrations and release, supporting the hypothesis that PVL could induce a neurogenic inflammation in the retina.

journal_name

Invest Ophthalmol Vis Sci

journal_title

Investigative ophthalmology & visual science

authors

Wurtz M,Ruhland E,Liu X,Namer IJ,Mazzoleni V,Lipsker D,Keller D,Prévost G,Gaucher D

doi

10.1167/iovs.62.1.4

subject

Has Abstract

pub_date

2021-01-04 00:00:00

pages

issue

eissn

0146-0404

issn

1552-5783

pii

2772143

journal_volume

pub_type

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Panton-Valentine Leucocidin of Staphylococcus aureus Induces Oxidative Stress and Neurotransmitter Imbalance in a Retinal Explant Model.