Panton‐Valentine leukocidin enhances glial reaction and microglial apoptosis through retinal ganglion and amacrine cell binding

Abstract

PurposePanton‐Valentine leukocidin (PVL) may be a critical virulence factor of S. aureus during endophthalmitis. This study aimed to identify the retinal cell targets for PVL, and to analyze early retinal changes during infectionMethodsAfter intravitreous PVL injection, adult rabbits were put down at different time points (30 min, 1, 2 and 4 h). PVL location in retina, its binding receptor C5aR, changes of Müller cells and microglial cells were analyzed using immunohistochemistry in the vertical sections or whole mounted retinas.ResultsIn rabbit retina, only ganglion cells clearly were shown to express C5aR. PVL increasingly bound retinal ganglion cells (RGCs) with time, reaching 98% of labeled cells after 2 h of PVL presence. Displaced amacrine cells (DACs) did not express C5aR, but transiently bound PVL from 68% to 5% between 30 min to 4 h. Müller cells abnormally expressed Glial Fibrillary Acid Protein in external retina compared with controls. Microglial cells body and dendrites were enlarged and dendritic processes sensibly decreased at 2 h and even disappeared at 4h. At 4 h following PVL injection, both immunohistochemistry and Western blot showed that some microglial cells underwent apoptosis and nitrotyrosine accumulated in retina.ConclusionsIn this model of PVL eye infection, PVL rapidly binds two kinds of retinal neural cells: RGCs possibly through C5aR interaction, DACs through an unknown mechanism. Müller cells and microglial cells were activated very early during the PVL binding process, suggesting an inflammatory cross‐talk between retinal neural cells and glial cells. Some microglial cells underwent apoptosis after 4 h PVL infection, at least associated to an abnormal production of nitrotyrosine in the retina.