PMID- 27732109
OWN - NLM
STAT- MEDLINE
DCOM- 20171204
LR  - 20180430
IS  - 1460-2202 (Electronic)
IS  - 0271-3683 (Linking)
VI  - 42
IP  - 5
DP  - 2017 May
TI  - Ischemia Reperfusion Injury Triggers TNFalpha Induced-Necroptosis in Rat Retina.
PG  - 771-779
LID - 10.1080/02713683.2016.1227449 [doi]
AB  - PURPOSE: A recent study revealed a novel form of cell death, termed necroptosis, 
      or programmed necrosis. Previous research indicated that after 
      ischemia-reperfusion (IR) injury to the retina, Tumor Necrosis Factor alpha (TNFalpha) is 
      increased, which may activate necroptosis. This study observed macroglial cell 
      activation, and in particular, astrocyte activation, after the release of TNFalpha 
      and other necroptosis factors in the rat retina due to IR. MATERIALS AND METHODS: 
      IR was induced in the retinas of adult male Sprague-Dawley rats by increasing the 
      intraocular pressure to 160 mmHg and then allowing reperfusion. In addition, to 
      inhibit necroptosis, Nec-1 (necrostatin-1) was injected intravitreally after IR. 
      Rats were sacrificed after reperfusion at 12 hours, 1, 3, and 5 days, and 1 and 2 
      weeks. Retinas from each time point were analyzed by immunohistochemistry (IHC) 
      and Western blotting (WB) to identify the initiator of necroptosis, TNFalpha, the 
      expression of necroptosis factors, such as receptor interacting protein (RIP) 1, 
      3, and inactive caspase 8, and Brn3a. RESULTS: Cell death in the IR-injured 
      retinas was identified by cell counting. We found decreased retinal cell numbers 
      in the inner and outer nuclear layers (INL and ONL), as well as in the ganglion 
      cell layer (GCL). Increased glial cell activation was detected by using glial 
      fibrillary acidic protein (GFAP) IHC. TNFalpha, RIP1, RIP3, and inactive caspase 8 
      were mainly expressed in the GCL after IR, as determined by IHC and WB. Nec-1 
      inhibited RIP1, a necroptosis factor, indicating protection against retinal cell 
      loss after IR injury. CONCLUSIONS: We showed that IR injury triggered increases 
      in both activation of astrocytes and the expression of TNFalpha. In addition, TNFalpha, 
      which was activated by IR, triggered the release of necroptosis factors, 
      particularly, in GCL. Inhibition of necroptosis using Nec-1 decreased the level 
      of RIP1 and retinal cell loss in IR-injured retinas.
FAU - Kim, Cho Rong
AU  - Kim CR
AD  - a Department of Ophthalmology and Visual Science , Seoul St. Mary's Hospital, 
      College of Medicine, The Catholic University of Korea , Seoul , Korea.
FAU - Kim, Jie Hyun
AU  - Kim JH
AD  - a Department of Ophthalmology and Visual Science , Seoul St. Mary's Hospital, 
      College of Medicine, The Catholic University of Korea , Seoul , Korea.
FAU - Park, Hae-Young Lopilly
AU  - Park HL
AD  - a Department of Ophthalmology and Visual Science , Seoul St. Mary's Hospital, 
      College of Medicine, The Catholic University of Korea , Seoul , Korea.
FAU - Park, Chan Kee
AU  - Park CK
AD  - a Department of Ophthalmology and Visual Science , Seoul St. Mary's Hospital, 
      College of Medicine, The Catholic University of Korea , Seoul , Korea.
LA  - eng
PT  - Journal Article
DEP - 20161012
PL  - England
TA  - Curr Eye Res
JT  - Current eye research
JID - 8104312
RN  - 0 (Imidazoles)
RN  - 0 (Indoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (necrostatin-1)
SB  - IM
MH  - Animals
MH  - *Apoptosis
MH  - Blotting, Western
MH  - Disease Models, Animal
MH  - Imidazoles/*pharmacology
MH  - Immunohistochemistry
MH  - Indoles/*pharmacology
MH  - Male
MH  - Necrosis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reperfusion Injury/*complications/diagnosis/metabolism
MH  - Retina/drug effects/*pathology
MH  - Retinal Diseases/diagnosis/*etiology/metabolism
MH  - Tumor Necrosis Factor-alpha/toxicity
OTO - NOTNLM
OT  - Ganglion cell layer
OT  - TNFalpha
OT  - ischemia-reperfusion
OT  - necroptosis
OT  - necrostatin-1
EDAT- 2016/10/13 06:00
MHDA- 2017/12/05 06:00
CRDT- 2016/10/13 06:00
PHST- 2016/10/13 06:00 [pubmed]
PHST- 2017/12/05 06:00 [medline]
PHST- 2016/10/13 06:00 [entrez]
AID - 10.1080/02713683.2016.1227449 [doi]
PST - ppublish
SO  - Curr Eye Res. 2017 May;42(5):771-779. doi: 10.1080/02713683.2016.1227449. Epub 
      2016 Oct 12.