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Moran Friedman Gohas, Shirel Weiss, Nitza Goldenberg-Cohen; Paradoxical neuroprotective effect induced by a single intravitreal injection of TNF-α following optic nerve crush. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5185.
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Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine produced by macrophages and T-cells. It plays an important role both in inflammation and apoptosis. In the eye, TNF-α appears to enhance apoptosis following trauma or inflammation. As predicted, TNFR1/2 knockout mice showed resistance to optic nerve crush (ONC) damage. Here we report a paradoxical neuroprotection effect of a single intravitreal injection (IVT) of TNF-α following ONC induction.
Histological analysis of wild type (WT) mice, with/without IVT TNF-α injection following ONC (n=5 each). Retinal thickness and the number of RGCs were measured. ONC was performed to the right eye only and the left eye served as control. Immunofluorescent staining with CD45, Vimentin and GFAP was used to demonstrate inflammatory reaction.
Histologically, RGCs count revealed preserved RGCs in the retinae of the TNF-α injected group as compared to the control ONC induced mice. WT group dropped by 6.6% in RGC’s count in comparison to the healthy eye, whereas the TNF-α injected group showed similar count and lost only 1.6%. Furthermore, retinal thickness of the control group lost 18.6% as compared to the treated group which lost 6.4%.
Previously, we showed that TNFR1/2 KO mice were resistant to ONC damage. Molecularly we showed increased TNF-α expression levels We assumed the lack of receptors blocks its proapoptotic effect. In this study, against expectations, IVT injection of TNF-α induced a neuroprotective effect. A possible mode of action is associated with decreased inflammation response. We assume that high dosage of TNF-α might suppress TNF-α receptors function and can cause a paradoxical nueroprotective effect. The immunomodulatory role in the inflammatory response following ONC is based on the balance between too low to over expression of TNF-α. As TNF-α inhibitors are used as neuroprotective drugs, the benefits and risks of the use of TNF-α or TNF-α blockers is not completely understood and yet to be explored.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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