PMID- 29084331
OWN - NLM
STAT- MEDLINE
DCOM- 20171102
LR  - 20180316
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 58
IP  - 12
DP  - 2017 Oct 1
TI  - The Anti-Inflammatory Effect of Ripasudil (K-115), a Rho Kinase (ROCK) Inhibitor,
      on Endotoxin-Induced Uveitis in Rats.
PG  - 5584-5593
LID - 10.1167/iovs.17-22679 [doi]
AB  - Purpose: To investigate the anti-inflammatory properties of ripasudil, a Rho
      kinase (ROCK) inhibitor, using endotoxin-induced uveitis (EIU) in rats. Methods: 
      Endotoxin-induced uveitis was induced by footpad injection of lipopolysaccharide 
      (LPS). Ripasudil was administered intraperitoneally 1 hour before and after LPS
      injection. The aqueous humor was collected 24 hours after injection, and the
      infiltrating cells, protein concentration, and levels of monocyte chemotactic
      protein-1 (MCP-1) were determined. Infiltrating cells in the iris ciliary body
      (ICB) and adherent leukocytes in retinal vessels were evaluated. The mRNA levels 
      of IL-1beta, IL-6, TNF-alpha, and MCP-1 in the retina and ICB were determined. A 
      mouse macrophage cell line, RAW264.7, was stimulated with LPS in the presence or 
      absence of ripasudil, and the expression of MCP-1 and nuclear translocation of
      nuclear factor (NF)-kappaB was analyzed. Results: Ripasudil significantly reduced
      infiltrating cells and protein exudation in the aqueous humor, as well as the
      number of infiltrating cells in the ICB and adherent leukocytes in retinal
      vessels in EIU. Additionally, the protein level of MCP-1 in the aqueous humor and
      mRNA levels of IL-1beta, IL-6, TNF-alpha, MCP-1, and intercellular adhesion
      molecule-1 in the ICB and retina were suppressed by ripasudil. The production of 
      MCP-1 and nuclear translocation of NF-kappaB in RAW264.7 cells were also
      suppressed by ripasudil. Conclusions: The Rho/ROCK pathway plays a role in
      adhesion molecule expression and inflammatory cell infiltration in EIU, and
      ripasudil is a potent anti-inflammatory agent against ocular inflammatory
      diseases, including acute uveitis and possibly uveitic glaucoma.
FAU - Uchida, Takatoshi
AU  - Uchida T
AD  - Department of Ophthalmology, Graduate School of Medicine, the University of
      Tokyo, Japan.
FAU - Honjo, Megumi
AU  - Honjo M
AD  - Department of Ophthalmology, Graduate School of Medicine, the University of
      Tokyo, Japan.
FAU - Yamagishi, Reiko
AU  - Yamagishi R
AD  - Department of Ophthalmology, Graduate School of Medicine, the University of
      Tokyo, Japan.
FAU - Aihara, Makoto
AU  - Aihara M
AD  - Department of Ophthalmology, Graduate School of Medicine, the University of
      Tokyo, Japan.
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 (Cytokines)
RN  - 0 (Endotoxins)
RN  - 0 (Isoquinolines)
RN  - 0 (K-115)
RN  - 0 (Sulfonamides)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
SB  - IM
MH  - Animals
MH  - Aqueous Humor/*metabolism
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Endotoxins/toxicity
MH  - Injections, Intraperitoneal
MH  - Isoquinolines/*administration & dosage
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Retina/drug effects/metabolism/*pathology
MH  - Sulfonamides/*administration & dosage
MH  - Uveitis/chemically induced/*drug therapy/metabolism
MH  - rho-Associated Kinases/antagonists & inhibitors
EDAT- 2017/10/31 06:00
MHDA- 2017/11/03 06:00
CRDT- 2017/10/31 06:00
PHST- 2017/10/31 06:00 [entrez]
PHST- 2017/10/31 06:00 [pubmed]
PHST- 2017/11/03 06:00 [medline]
AID - 2661279 [pii]
AID - 10.1167/iovs.17-22679 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2017 Oct 1;58(12):5584-5593. doi:
      10.1167/iovs.17-22679.