PMID- 24754835
OWN - NLM
STAT- MEDLINE
DCOM- 20150330
LR  - 20211021
IS  - 1460-9568 (Electronic)
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 40
IP  - 3
DP  - 2014 Aug
TI  - The TIR-domain-containing adapter inducing interferon-beta-dependent signaling 
      cascade plays a crucial role in ischemia-reperfusion-induced retinal injury, 
      whereas the contribution of the myeloid differentiation primary response 
      88-dependent signaling cascade is not as pivotal.
PG  - 2502-12
LID - 10.1111/ejn.12603 [doi]
AB  - Toll-like receptor 4 (Tlr4) plays an important role in ischemia-reperfusion 
      (IR)-induced retinal inflammation and damage. However, the role of two 
      Tlr4-dependent signaling cascades, myeloid differentiation primary response 88 
      (Myd88) and TIR-domain-containing adapter inducing interferon-beta (Trif), in 
      retinal IR injury is poorly understood. In this study, we investigated the 
      contribution of the Myd88-dependent and Trif-dependent signaling cascades in 
      retinal damage and inflammation triggered by IR, by using Myd88 knockout 
      (Myd88KO) and Trif knockout (TrifKO) mice. Retinal IR injury was induced by 
      unilateral elevation of intraocular pressure for 45 min by direct corneal 
      cannulation. To study IR-induced retinal ganglion cell (RGC) death in vitro, we 
      used an oxygen and glucose deprivation (OGD) model. Our data suggested that Myd88 
      was present in many retinal layers of sham-operated and ischemic mice, whereas 
      Trif was mainly present in the ganglion cell layer (GCL). The level of Myd88 was 
      increased in the retina after IR. We found that retinas of TrifKO mice had a 
      significantly reduced neurotoxic pro-inflammatory response and significantly 
      increased survival of the GCL neurons after IR. Although Myd88KO mice had 
      relatively low levels of inflammation in ischemic retinas, their levels of 
      IR-induced retinal damage were notably higher than those of TrifKO mice. We also 
      found that Trif-deficient RGCs were more resistant to death induced by OGD than 
      were RGCs isolated from Myd88KO mice. These data suggested that, as compared with 
      the Myd88-dependent signaling cascade, Trif signaling contributes significantly 
      to retinal damage after IR.
CI  - (c) 2014 The Authors. European Journal of Neuroscience published by Federation of 
      European Neuroscience Societies and John Wiley & Sons Ltd.
FAU - Dvoriantchikova, Galina
AU  - Dvoriantchikova G
AD  - Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami 
      Miller School of Medicine, 1638 NW 10th Ave, Miami, FL, 33136, USA.
FAU - Santos, Andrea Rachelle C
AU  - Santos AR
FAU - Danek, Dagmara
AU  - Danek D
FAU - Dvoriantchikova, Xenia
AU  - Dvoriantchikova X
FAU - Ivanov, Dmitry
AU  - Ivanov D
LA  - eng
GR  - P30 EY014801/EY/NEI NIH HHS/United States
GR  - R01 EY022348/EY/NEI NIH HHS/United States
GR  - P30EY014801/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20140423
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Myd88 protein, mouse)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/genetics/*metabolism
MH  - Animals
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myeloid Differentiation Factor 88/genetics/*metabolism
MH  - Reperfusion Injury/metabolism
MH  - Retina/metabolism
MH  - Retinal Diseases/*metabolism
MH  - Retinal Ganglion Cells/metabolism
MH  - Retinitis/*metabolism
MH  - *Signal Transduction
MH  - Toll-Like Receptor 4/*metabolism
PMC - PMC4122625
MID - NIHMS583330
OTO - NOTNLM
OT  - inflammation
OT  - ischemia-reperfusion injury
OT  - mouse models
OT  - retinal damage
OT  - toll-like receptor signaling
EDAT- 2014/04/24 06:00
MHDA- 2015/03/31 06:00
CRDT- 2014/04/24 06:00
PHST- 2014/02/19 00:00 [received]
PHST- 2014/03/25 00:00 [revised]
PHST- 2014/03/28 00:00 [accepted]
PHST- 2014/04/24 06:00 [entrez]
PHST- 2014/04/24 06:00 [pubmed]
PHST- 2015/03/31 06:00 [medline]
AID - 10.1111/ejn.12603 [doi]
PST - ppublish
SO  - Eur J Neurosci. 2014 Aug;40(3):2502-12. doi: 10.1111/ejn.12603. Epub 2014 Apr 23.