PMID- 32321985
OWN - NLM
STAT- MEDLINE
DCOM- 20201116
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 100
IP  - 8
DP  - 2020 Aug
TI  - Histone H2B induces retinal ganglion cell death through toll-like receptor 4 in 
      the vitreous of acute primary angle closure patients.
PG  - 1080-1089
LID - 10.1038/s41374-020-0427-2 [doi]
AB  - Acute primary angle closure (APAC) is a disease of ophthalmic urgency; lack of 
      treatment can lead to blindness. Even after adequate treatment for APAC, 
      subsequent elevated acute intraocular pressure induces severe neuronal damage 
      which can result in secondary glaucomatous optic neuropathy (GON). 
      Damage-associated molecular patterns (DAMPs) are released from damaged and dead 
      neuronal cells, which induce secondary inflammatory changes and further tissue 
      damage. Our hypothesis is that histone H2B (H2B), which is one of the DAMPs, is 
      released from damaged cells in the development of GON after APAC treatment. 
      Intravitreal injection of H2B induces neuronal cell death through toll-like 
      receptor 4 (TLR4) expression, following the upregulation of inflammatory cytokine 
      mRNAs and phosphorylation of mitogen activated protein kinases (MAPKs). Knockdown 
      of TLR4 caused a reduction of H2B neurotoxicity in damaged cells through TLR4 
      signaling. Significantly increased H2B was observed in the vitreous cells of APAC 
      patients. In addition, enhanced H2B protein correlated with decreased ganglion 
      cell analysis and retinal ganglion cell (RGC) layer thinning, which indicates the 
      effect of H2B on RGCs. Our data from clinical and animal studies show the 
      involvement of H2B-TLR4 pathways in the development of GON after APAC treatment 
      providing new insight for the mechanism of RGC degeneration.
FAU - Munemasa, Yasunari
AU  - Munemasa Y
AD  - Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 
      Sugao Miyamae, Kawasaki, Kanagawa, 2168511, Japan. munemasay@gmail.com.
LA  - eng
PT  - Journal Article
DEP - 20200422
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Cytokines)
RN  - 0 (Histones)
RN  - 0 (Toll-Like Receptor 4)
SB  - IM
MH  - Aged
MH  - Animals
MH  - Cell Death
MH  - Cytokines/genetics/metabolism
MH  - Female
MH  - Gene Expression Regulation
MH  - Histones/administration & dosage
MH  - Humans
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Optic Nerve Diseases/genetics/*metabolism/pathology
MH  - Retina/drug effects/metabolism
MH  - Retinal Ganglion Cells/cytology/*metabolism
MH  - Toll-Like Receptor 4/genetics/*metabolism
MH  - Vitreous Body/*metabolism/pathology
PMC - PMC7374083
COIS- The author declares no conflict of interest.
EDAT- 2020/04/24 06:00
MHDA- 2020/11/18 06:00
PMCR- 2020/04/22
CRDT- 2020/04/24 06:00
PHST- 2019/10/31 00:00 [received]
PHST- 2020/03/29 00:00 [accepted]
PHST- 2020/03/29 00:00 [revised]
PHST- 2020/04/24 06:00 [pubmed]
PHST- 2020/11/18 06:00 [medline]
PHST- 2020/04/24 06:00 [entrez]
PHST- 2020/04/22 00:00 [pmc-release]
AID - S0023-6837(22)00375-0 [pii]
AID - 427 [pii]
AID - 10.1038/s41374-020-0427-2 [doi]
PST - ppublish
SO  - Lab Invest. 2020 Aug;100(8):1080-1089. doi: 10.1038/s41374-020-0427-2. Epub 2020 
      Apr 22.