Panton-Valentine Leukocidin Colocalizes with Retinal Ganglion and Amacrine Cells and Activates Glial Reactions and Microglial Apoptosis

潘顿-瓦伦丁白细胞毒素与视网膜神经节和无长突细胞共定位并激活神经胶质反应和小胶质细胞凋亡

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作者:XuanLi Liu, Pauline Heitz, Michel Roux, Daniel Keller, Tristan Bourcier, Arnaud Sauer, Gilles Prévost, David Gaucher

Abstract

Experimental models have established Panton-Valentine leukocidin (PVL) as a potential critical virulence factor during Staphylococcus aureus endophthalmitis. In the present study, we aimed to identify retinal cell targets for PVL and to analyze early retinal changes during infection. After the intravitreous injection of PVL, adult rabbits were euthanized at different time points (30 min, 1, 2, 4 and 8 h). PVL location in the retina, expression of its binding receptor C5a receptor (C5aR), and changes in Müller and microglial cells were analyzed using immunohistochemistry, Western blotting and RT-qPCR. In this model of PVL eye intoxication, only retinal ganglion cells (RGCs) expressed C5aR, and PVL was identified on the surface of two kinds of retinal neural cells. PVL-linked fluorescence increased in RGCs over time, reaching 98% of all RGCs 2 h after PVL injection. However, displaced amacrine cells (DACs) transiently colocalized with PVL. Müller and microglial cells were increasingly activated after injection over time. IL-6 expression in retina increased and some microglial cells underwent apoptosis 4 h and 8 h after PVL infection, probably because of abnormal nitrotyrosine production in the retina.

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