Microglial TIR-domain-containing adapter-inducing interferon-β (TRIF) deficiency promotes retinal ganglion cell survival and axon regeneration via nuclear factor-κB.

Journal of Neuroinflammation
Sen LinBingyin Su

Abstract

TIR-domain-containing adapter-inducing interferon-β (TRIF) is the sole downstream adaptor of Toll-like receptor (TLR)3, which is one of the major signaling pathways in immune cells leading to neuroinflammation in the central nervous system. Overexpression of TRIF may lead to activation of inflammatory responses, and contribute to pathophysiological progression in both acute and chronic neurodegenerative retinal diseases. In the present study, was aimed to elucidate the contributions of TRIF to optic nerve (ON) regeneration and retinal ganglion cell (RGC) survival following injury to the ON, a widely studied model of central nervous system injury and of degenerative diseases such as glaucoma. We used retrograde labeling with a fluorochrome, hydroxystilbamidine (Fluorogold) to evaluate RGC survival, and immunostaining with growth-associated protein-43 to evaluate axon regeneration in an ON crush model. Changes in microglial cytokines following RGC injury was examined with ELISA and real-time PCR. In vivo studies were carried out in wild-type and trif-/- mice. A Transwell co-culture system and migration test were used to mimic the crosstalk between microglia and RGCs. TRIF-associated downstream adaptors were determined by western ...Continue Reading

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Citations

Aug 15, 2014·Journal of Neuroinflammation·Neal D HeussDale S Gregerson
Feb 3, 2015·Frontiers in Physiology·Joseph M RifkindEnika Nagababu
Dec 30, 2017·Molecular Medicine Reports·Nanye WangGuodong Li
Sep 29, 2020·Restorative Neurology and Neuroscience·Yimeng Lina DuDonald G Stein
Jul 25, 2018·Acta Neuropathologica Communications·Neal D HeussDale S Gregerson
Nov 5, 2019·Frontiers in Cell and Developmental Biology·Wenyi LiuJian Ye
Jun 2, 2020·Frontiers in Cellular Neuroscience·Shu-Guang YangFeng-Quan Zhou

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Methods Mentioned

BETA
protein assay
PCR
protein
ELISA
enzyme-linked immunosorbent assay

Software Mentioned

Image Pro Plus
SPSS
GraphPad
Graph Pad PRISM

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