PMID- 20847117
OWN - NLM
STAT- MEDLINE
DCOM- 20110225
LR  - 20161125
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 52
IP  - 1
DP  - 2011 Jan 21
TI  - Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in 
      a mouse corneal alkali-burn model.
PG  - 427-33
LID - 10.1167/iovs.10-6167 [doi]
AB  - PURPOSE: To investigate the role of reactive oxygen species (ROS) as the prime 
      initiators of the angiogenic response after alkali injury of the cornea and 
      observe the effects of antioxidants in preventing angiogenesis. METHODS: The 
      corneal epithelia of SOD-1-deficient mice or wild-type (WT) mice were removed 
      after application of 0.15 N NaOH to establish the animal model of alkali burn. 
      ROS production was semiquantitatively measured by dihydroethidium (DHE) 
      fluorescence. Angiogenesis was visualized by CD31 immunohistochemistry. The 
      effects of the specific NF-kappaB inhibitor DHMEQ, the antioxidant 
      N-acetyl-L-cysteine (NAC), and hydrogen (H2) solution were observed. RESULTS: ROS 
      production in the cornea was enhanced immediately after alkali injury, as shown 
      by increased DHE fluorescence (P<0.01). NF-kappaB activation and the upregulation of 
      vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 
      (MCP-1) were significantly enhanced (P<0.01), leading to a significantly larger 
      area of angiogenesis. Angiogenesis in SOD-1-/- mice corneas were significantly 
      higher in WT mice (P<0.01), confirming the role of ROS. Pretreatment with the 
      specific NF-kappaB inhibitor DHMEQ or the antioxidant NAC significantly reduced 
      corneal angiogenesis by downregulating the NF-kappaB pathway (P<0.01) in both WT and 
      SOD-1-/- mice. Furthermore, we showed that irrigation of the cornea with hydrogen 
      (H2) solution significantly reduced angiogenesis after alkali-burn injury 
      (P<0.01). CONCLUSIONS: Immediate antioxidant therapy with H2-enriched irrigation 
      solution is a new potent treatment of angiogenesis in cornea to prevent blindness 
      caused by alkali burn.
FAU - Kubota, Miyuki
AU  - Kubota M
AD  - Department of Ophthalmology, Keio University School of Medicine, Shinjuku-ku, 
      Tokyo, Japan.
FAU - Shimmura, Shigeto
AU  - Shimmura S
FAU - Kubota, Shunsuke
AU  - Kubota S
FAU - Miyashita, Hideyuki
AU  - Miyashita H
FAU - Kato, Naoko
AU  - Kato N
FAU - Noda, Kousuke
AU  - Noda K
FAU - Ozawa, Yoko
AU  - Ozawa Y
FAU - Usui, Tomohiko
AU  - Usui T
FAU - Ishida, Susumu
AU  - Ishida S
FAU - Umezawa, Kazuo
AU  - Umezawa K
FAU - Kurihara, Toshihide
AU  - Kurihara T
FAU - Tsubota, Kazuo
AU  - Tsubota K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110121
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (Antioxidants)
RN  - 0 (Benzamides)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cyclohexanones)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (dehydroxymethylepoxyquinomicin)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - 55X04QC32I (Sodium Hydroxide)
RN  - EC 1.15.1.1 (Sod1 protein, mouse)
RN  - EC 1.15.1.1 (Superoxide Dismutase)
RN  - EC 1.15.1.1 (Superoxide Dismutase-1)
RN  - J65BV539M3 (Deuterium Oxide)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/administration & dosage/*therapeutic use
MH  - Animals
MH  - Antioxidants/administration & dosage/*therapeutic use
MH  - Benzamides/pharmacology
MH  - Blindness/prevention & control
MH  - Burns, Chemical/*drug therapy/metabolism/pathology
MH  - Chemokine CCL2/metabolism
MH  - Corneal Neovascularization/*drug therapy/metabolism/pathology
MH  - Cyclohexanones/pharmacology
MH  - Deuterium Oxide/administration & dosage/*therapeutic use
MH  - *Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Eye Burns/*chemically induced
MH  - Male
MH  - Mice
MH  - Mice, Inbred ICR
MH  - Mice, Knockout
MH  - Microscopy, Fluorescence
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sodium Hydroxide/toxicity
MH  - Superoxide Dismutase/genetics
MH  - Superoxide Dismutase-1
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2010/09/18 06:00
MHDA- 2011/02/26 06:00
CRDT- 2010/09/18 06:00
PHST- 2010/09/18 06:00 [entrez]
PHST- 2010/09/18 06:00 [pubmed]
PHST- 2011/02/26 06:00 [medline]
AID - iovs.10-6167 [pii]
AID - 10.1167/iovs.10-6167 [doi]
PST - epublish
SO  - Invest Ophthalmol Vis Sci. 2011 Jan 21;52(1):427-33. doi: 10.1167/iovs.10-6167.