Document Detail

Effects of unoprostone on phosphorylated extracellular signal-regulated kinase expression in endothelin-1-induced retinal and optic nerve damage.
MedLine Citation:
PMID:  18442442     Owner:  NLM     Status:  MEDLINE    
Endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been implicated in the development of normal- and high-tension glaucoma. We investigated the effects of unoprostone on extracellular signal-regulated kinase (ERK) in ET-1-induced retinal ganglion cell (RGC) death and optic nerve injury. Our morphometric study showed that intravitreal injection of ET-1 led to cell loss in the RGC layer (RGCL) in 28 days. Western blot analysis showed decreased neurofilament (NF) protein in the optic nerve 28 days after ET-1 injection. In this in vivo model, increased phosphorylated ERK (p-ERK) was observed in the retina on 1 day and subsequently in the optic nerve from 7 days after ET-1 injection. Simultaneous injection of M1, as a metabolite of unoprostone, showed further increased p-ERK levels compared with ET-1 injection alone. Our morphometric study of flat-mount preparations stained with cresyl violet or retrograde labeling with a neuro-tracer and Western blot analysis of NF showed that inhibition of ERK phosphorylation led to acceleration of ET-1-induced RGC death and optic nerve damage. In addition, M1 significantly attenuated both RGC loss and the decrease in NF protein induced by ET-1. The protective effects of M1 were significantly inhibited by U0126, an ERK inhibitor. These results suggest that unoprostone has neuroprotective effects against ET-1-induced neuronal injury through ERK phosphorylation.
Yasunari Munemasa; Yasushi Kitaoka; Yasuhiro Hayashi; Hiroyuki Takeda; Hiromi Fujino; Ritsuko Ohtani-Kaneko; Kazuaki Hirata; Satoki Ueno
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Visual neuroscience     Volume:  25     ISSN:  1469-8714     ISO Abbreviation:  Vis. Neurosci.     Publication Date:    2008 Mar-Apr
Date Detail:
Created Date:  2008-04-29     Completed Date:  2008-05-19     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8809466     Medline TA:  Vis Neurosci     Country:  England    
Other Details:
Languages:  eng     Pagination:  197-208     Citation Subset:  IM    
Department of Ophthalmology, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa 216-8511, Japan.
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MeSH Terms
Blotting, Western
Cell Death
Dinoprost / analogs & derivatives*,  pharmacology
Endothelin-1 / pharmacology*
Extracellular Signal-Regulated MAP Kinases / metabolism*
Neurofilament Proteins / antagonists & inhibitors
Neuroprotective Agents / pharmacology*
Optic Nerve / drug effects*,  enzymology,  metabolism,  pathology
Rats, Wistar
Retina / drug effects*,  enzymology,  pathology
Retinal Ganglion Cells / drug effects,  pathology
Reg. No./Substance:
0/Endothelin-1; 0/Neurofilament Proteins; 0/Neuroprotective Agents; 108688-71-7/neurofilament protein H; 551-11-1/Dinoprost; 69553-75-9/isopropyl unoprostone; EC Signal-Regulated MAP Kinases

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