IOVS
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

(Investigative Ophthalmology and Visual Science. 2005;46:4072-4078.)
© 2005 by The Association for Research in Vision and Ophthalmology, Inc.
doi:10.1167/iovs.05-0105
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow An erratum has been published
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Berdugo, M.
Right arrow Articles by Behar-Cohen, F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Berdugo, M.
Right arrow Articles by Behar-Cohen, F.

Downregulation of IRS-1 Expression Causes Inhibition of Corneal Angiogenesis

Marianne Berdugo,1,2 Charlotte Andrieu-Soler,1,2,3 Marc Doat,1 Yves Courtois,1 David BenEzra,4 and Francine Behar-Cohen1,5

1From the Institut National de la Santé et de la Recherche Médicale (INSERM), U598, Paris, France; 3Optis France, Paris, France; 4Hadassah Hebrew University Hospital, Jerusalem, Israel; and the 5Rothschild Foundation, Paris, France.

PURPOSE. The antiangiogenic effect of an antisense oligodeoxynucleotide (ODN) targeting insulin receptor substrate (IRS)-1 was evaluated on rat corneal neovascularization.

METHODS. Eyes with neovessels were treated with subconjunctival injections of IRS-1 antisense oligonucleotide (ASODN), IRS-1 sense ODN (SODN), or PBS. At 8 and 24 hours after the first subconjunctival injection, the expression of IRS-1, VEGF, and IL-1ß mRNA was evaluated. IRS-1 protein levels were also measured at 8 hours by Western blot analysis (n = 4/group). On day 10, corneal neovascularization was quantified in flatmount corneas of rats treated daily from days 4 to 9.

RESULTS. On day 10, new vessels covered 95.5% ± 4% of the corneal area in PBS-treated eyes, 92% ± 7% in SODN-treated eyes and 59% ± 20% in ASODN-treated eyes (P < 0.001). In the ASODN-treated group, the expression and synthesis of IRS-1 were significantly downregulated when compared with the control groups. ASODN did not significantly affect the expression of VEGF but significantly decreased the expression of IL-1ß at 24 hours (P = 0.04).

CONCLUSIONS. Subconjunctival injections of IRS-1 antisense ODN significantly inhibit rat corneal neovascularization. This effect may be mediated by a downregulation of IL-1ß. IRS-1 proteins may be interesting targets for the regulation of angiogenesis mediated by insulin, hypoxia, or inflammation.




This article has been cited by other articles:


Home page
 J. Pharmacol. Exp. Ther.Home page
S. Al-Mahmood, S. Colin, N. Farhat, E. Thorin, C. Steverlynck, and S. Chemtob
Potent in Vivo Antiangiogenic Effects of GS-101 (5'-TATCCGGAGGGCTCGCCATGCTGCT-3'), an Antisense Oligonucleotide Preventing the Expression of Insulin Receptor Substrate-1
J. Pharmacol. Exp. Ther., May 1, 2009; 329(2): 496 - 504.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2005 by the Association for Research in Vision and Ophthalmology