Panton-Valentine Leucocidin Proves Direct Neuronal Targeting and Its Early Neuronal and Glial Impacts a Rabbit Retinal Explant Model.

: Panton-Valentine leukocidin (PVL) retinal intoxication induces glial activation and inflammatory response via the interaction with retinal neurons. In this study, rabbit retinal explant was used as a model to study neuronal and glial consequences of PVL intoxication. Retinal explants were treated with different concentrations of PVL. PVL location and neuronal and glial changes were examined using immunohistochemistry. Some inflammatory factors were quantified using RT-qPCR at 4 and 8 h. These results were compared with those of control explants. PVL co-localized rapidly with retinal ganglion cells and with horizontal cells. PVL induced Müller and microglial cell activation. Retinal structure was altered and some amacrine and microglial cells underwent apoptosis. Glial activation and cell apoptosis increased in a PVL concentration- and time-dependent manner. IL-6 and IL-8 expression increased in PVL-treated explants but less than in control explants, which may indicate that other factors were responsible for glial activation and retinal apoptosis. On retinal explants, PVL co-localized with neuronal cells and induced glial activation together with microglial apoptosis, which confirms previous results observed in in vivo model. Rabbit retinal explant seems to be suitable model to further study the process of PVL leading to glial activation and retinal cells apoptosis.

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

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.

Diabetic retinopathy / Rétinopathie diabétique

Diabetic retinopathy. Diabetic retinopathy (DR) is a disease whose screening actually can change the functional prognosis for the patients. It makes blindness avoidable. Annual screening using funduscopy or retinography for all diabetic patients is mandatory and yet not sufficiently and systematically performed in France. French Public health authority is developping telemedicine screening programs in different french regions to improve the prevention of DR. The treatment of DR is based on the management of its 2 major complications, that can coexist: preretinal neovascular proliferation (proliferative diabetic retinopathy), and diabetic macular edema (DME). Both of these complications require preventive management through strict control of blood glucose, blood pressure and hyperlipidemia. Once the complication is present, PRP must be performed to treat the neovessels while antiVEGF or corticosteroids intravitreal injections are the best way to treat DME. Surgery is required for more complicated forms of DR, such as intra-vitreous haemorrhage, retinal detachment, or neovascular glaucoma.

Rétinopathie diabétique. La rétinopathie diabétique est une maladie dont le dépistage change véritablement le pronostic fonctionnel pour le patient. Il rend la cécité évitable. Le dépistage par rétinographie et/ ou fond d'oeil annuel pour tous les diabétiques n'est pas encore assez systématique, et la Haute Autorité de santé cherche à développer des programmes de dépistage par télémédecine au niveau régional. Le traitement de la rétinopathie diabétique repose sur le traitement de ses deux complications majeures qui peuvent coexister : la prolifération néovasculaire, et l'oedème maculaire diabétique. Ces deux complications nécessitent une prise en charge préventive par un contrôle strict de la glycémie, de la pression artérielle et de l'hyperlipidémie. Une fois la complication avérée, la photocoagulation panrétinienne reste le traitement des néovaisseaux et les injections d'anti-VEGF, voire de corticoïdes, ceux de l'oedème maculaire diabétique. La chirurgie devient inévitable pour les formes compliquées, comme les hémorragies intravitréennes, les décollements de rétine ou le glaucome néovasculaire.