PMID- 32749463
OWN - NLM
STAT- MEDLINE
DCOM- 20210101
LR  - 20210101
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Print)
IS  - 0146-0404 (Linking)
VI  - 61
IP  - 10
DP  - 2020 Aug 3
TI  - Effects of ROCK Inhibitors on Apoptosis of Corneal Endothelial Cells in 
      CMV-Positive Posner-Schlossman Syndrome Patients.
PG  - 5
LID - 10.1167/iovs.61.10.5 [doi]
LID - 5
AB  - PURPOSE: To examine the role of aqueous tumor necrosis factor alpha (TNF-alpha)-RhoA-Rho 
      kinase (ROCK) signaling in cytomegalovirus (CMV)-induced apoptosis and the 
      barrier function of cultured human corneal endothelial cells (hCECs) in 
      CMV-positive Posner-Schlossman syndrome (CMV+/PSS) patients. METHODS: Aqueous 
      levels of TNF-alpha, IL-8, IL-10, and several other cytokines in 19 CMV+/PSS patients 
      and 20 healthy control subjects were quantitated using a multiplex assay. The 
      expression of active RhoA in hCECs post-CMV infection was determined using 
      western blotting (WB). The expression levels of TNF-alpha and nuclear factor kappa B 
      (NF-kappaB) in CMV-infected hCECs were examined by immunocytochemistry (ICC) and WB 
      with and without ROCK inhibitors. The apoptotic rate and barrier integrity in 
      CMV-infected hCECs were also examined. RESULTS: The expression levels of TNF-alpha, 
      monocyte chemoattractant protein-1 (MCP-1), IL-8, and IL-10 were upregulated in 
      the aqueous humor of CMV+/PSS patients, and among these upregulated cytokines 
      aqueous TNF-alpha was negatively correlated with the number of corneal endothelial 
      cells. In CMV-infected hCECs, upregulation of TNF-alpha and NF-kappaB was determined by 
      WB and ICC. In hCECs, CMV infection induced apoptosis and significantly impaired 
      cell-cell contacts, effects that were attenuated by treatment with a ROCK 
      inhibitor. CONCLUSIONS: Aqueous TNF-alpha was upregulated in CMV+/PSS patients, which 
      may have triggered corneal endothelial cell loss. Modulation of TNF-alpha, including 
      its downstream Rho-ROCK signaling, could serve as a novel treatment modality for 
      corneal endothelial cell loss in CMV+/PSS patients.
FAU - Igarashi, Nozomi
AU  - Igarashi N
AD  - ,.
FAU - Honjo, Megumi
AU  - Honjo M
AD  - ,.
FAU - Kaburaki, Toshikatsu
AU  - Kaburaki T
AD  - ,.
FAU - Aihara, Makoto
AU  - Aihara M
AD  - ,.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Amides)
RN  - 0 (Cytokines)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Isoquinolines)
RN  - 0 (K-115)
RN  - 0 (Pyridines)
RN  - 0 (Sulfonamides)
RN  - 138381-45-0 (Y 27632)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.6.5.2 (rhoA GTP-Binding Protein)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amides/pharmacology
MH  - Apoptosis/*drug effects
MH  - Aqueous Humor/metabolism/virology
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Cytomegalovirus/isolation & purification
MH  - Cytomegalovirus Infections/metabolism/*pathology/virology
MH  - Endothelium, Corneal/metabolism/*pathology/virology
MH  - Enzyme Inhibitors/*pharmacology
MH  - Eye Infections, Viral/metabolism/*pathology/virology
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Iridocyclitis/metabolism/*pathology/virology
MH  - Isoquinolines/pharmacology
MH  - Male
MH  - Middle Aged
MH  - Multiplex Polymerase Chain Reaction
MH  - Prospective Studies
MH  - Pyridines/pharmacology
MH  - Sulfonamides/pharmacology
MH  - rho-Associated Kinases/*antagonists & inhibitors
MH  - rhoA GTP-Binding Protein/metabolism
PMC - PMC7441372
COIS- Disclosure: N. Igarashi, None; M. Honjo, None; T. Kaburaki, None; M. Aihara, None
EDAT- 2020/08/05 06:00
MHDA- 2021/01/02 06:00
PMCR- 2020/08/04
CRDT- 2020/08/05 06:00
PHST- 2020/08/05 06:00 [entrez]
PHST- 2020/08/05 06:00 [pubmed]
PHST- 2021/01/02 06:00 [medline]
PHST- 2020/08/04 00:00 [pmc-release]
AID - 2770570 [pii]
AID - IOVS-20-29492 [pii]
AID - 10.1167/iovs.61.10.5 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2020 Aug 3;61(10):5. doi: 10.1167/iovs.61.10.5.