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Synergistic effect of SP & IGF
The following articles were kindly provided by Researcher Takashi Nagano, of the Japanese Research and Development Centre of Santen Pharmaceutical Co. Ltd. You may find some articles on the Internet demonstrating the potential of the combined action of both substances to promote corneal healing in neurotrophic keratitis or epitheliophaty. Most of the following articles show an impovement of wound healing using the synergistic effect of Substance P and IGF. It seems that the improvement in terms of corneal sensitivity is transitory but the re-loss of sensation is not necessarely followed by relapses (corneal erosions).
Clinical trials in Japan on humans:
Neurotrophic and anhidrotic keratopathy
treated with substance P and insulinlike growth factor 1.
Arch Ophthalmol. 1997 Jul;115(7):926-7. (In this case, a total re-epithelialisation of a central corneal ulcer was achieved for the left eye using both substances ; the right eye, underwent a succesful keratoplasty using the same substances). http://www.ophthal.org/ORJ/plastics/vol3.shtml
Treatment of neurotrophic keratopathy
with substance-P-derived peptide (FGLM) and insulin-like growth factor I.
Lancet. 1998 Jun 13;351(9118):1783-4 (In this article, a total re-epithelialisation was achieved in 2 weeks; improvement of sensitivity was also achieved and progressively lost again but the renewed loss of sensitivity did not lead to the renewal of the erosions during the 5 months which followed the termination of the treatment).
In vivo trials in Japan on rabbits and rats:
Combined effects of substance P and
insulin-like growth factor-1 on corneal epithelial wound closure of rabbit in
Curr Eye Res. 1997 Mar;16(3):275-8
Synergistic effect with Phe-Gly-Leu-Met-NH2 of the C-terminal of substance P and insulin-like growth factor-1 on epithelial wound healing of rabbit cornea. Br J Pharmacol. 1999 May;127(2):489-97
Promotion of corneal epithelial wound healing in diabetic rats by the combination of a substance P-derived peptide (FGLM-NH2) and insulin-like growth factor-1. Diabetologia. 2003 Jun;46(6):839-42. Epub 2003 May 22
In vitro trials in Japan on human corneas and cells (articles n°3, 4 and 6), or on rats and rabbits corneal cells:
Synergistic effects of substance P with
insulin-like growth factor-1 on epithelial migration of the cornea.
J Cell Physiol. 1996 Oct;169(1):159-66.
The NK1 receptor and its participation
in the synergistic enhancement of corneal epithelial migration by substance P
and insulin-like growth factor-1.
Br J Pharmacol. 1997 Feb;120(4):547-52
Up-regulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells
Up-regulation of phosphorylation of focal adhesion kinase and paxillin by combination of substance P and IGF-1 in SV-40 transformed human corneal epithelial cells, Biochem Biophys Res Commun. 1998 Jan 6;242(1):16-20
Up-regulation of integrin alpha 5
expression by combination of substance P and insulin-like growth factor-1 in
rabbit corneal epithelial cells.
Biochem Biophys Res Commun. 1998 May 29;246(3):777-82
Up-regulation of integrin alpha5 by a C-terminus four-amino-acid sequence of substance P (phenylalanine-glycine-leucine-methionine- amide) synergistically with insulin-like growth factor-1 in SV-40 transformed human corneal epithelial cells, Biochem Biophys Res Commun. 1999 Feb 24;255(3):692-7.
Characterization of insulin-like growth
factor-1 receptors in rabbit corneal epithelial cells.
Exp Eye Res. 2000 Feb;70(2):199-204
Signaling regulation for synergistic
effects of substance P and insulin-like growth factor-1 or epidermal growth
factor on corneal epithelial migration.
Jpn J Ophthalmol. 2000 Jan-Feb;44(1):1-8
Other insteresting articles:
Futhermore, Dr. Nagano announced the publication of a study on several patients suffering from persistent epithelial defects treated by the combined effect of FGLM-NH2 (C-terminus of Substance P) and IGF-1 (Insulin-like Growth Factor), which reports very promising results.
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