Premium
Retinal cell type‐specific prevention of ischemia‐induced damages by LPS ‐ TLR 4 signaling through microglia
Author(s) -
Halder Sebok K.,
Matsunaga Hayato,
Ishii Ken J.,
Akira Shizuo,
Miyake Kensuke,
Ueda Hiroshi
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12262
Subject(s) - microglia , retina , retinal , ischemia , microbiology and biotechnology , retinal ganglion cell , pharmacology , ischemic preconditioning , medicine , chemistry , neuroscience , inflammation , biology , immunology , biochemistry
Reprogramming of toll‐like receptor 4 ( TLR 4) by brief ischemia or lipopolysacharide ( LPS ) contributes to superintending tolerance against destructive ischemia in brain. However, beneficial roles of TLR 4 signaling in ischemic retina are not well known. This study demonstrated that preconditioning with LPS 48 h prior to the retinal ischemia prevents the cellular damage in morphology with hematoxylin and eosin (H&E) staining and functions of retina with electroretinogram ( ERG ), while post‐ischemia treatment deteriorated it. The preventive effects of LPS preconditioning showed the cell type‐specificity of retinal cells. There was complete rescue of ganglion cells, partial rescue of bipolar and photoreceptor cells or no rescue of amacrine cells, respectively. LPS treatment caused the proliferation and migration of retinal microglia and its preconditioning prevented the ischemia‐induced microglial activation. Preventive actions from cell damages following LPS preconditioning prior to retinal ischemia were abolished in TLR 4 knock‐out mice, and by pre‐treatments with anti‐ TLR 4 antibody or minocycline, a microglia inhibitor, which themselves had no effects on the retinal ischemia‐induced damages or microglia activation. Thus, this study revealed that TLR 4 mediates the LPS preconditioning‐induced preventive effects through microglial activation in the retinal ischemia model.