Anti-SPARC oligopeptide inhibits laser-induced CNV in mice.
It is known that SPARC gates VEGF-A signal transduction towards KDR, the primary angiogenic VEGF receptor. We sought to determine whether inhibition of SPARC activity using anti-SPARC peptide could inhibit laser-induced CNV by promoting binding of VEGF-A to FLT-1. We created anti-SPARC l-peptide and retro-inverso anti-SPARC d-peptide. Anti-SPARC peptides or PBS were injected intravitreally 1day before or after laser induction. Intravitreal injection of anti-SPARC l-peptide 1day before laser induction promotes FLT-1 phosphorylation and inhibited laser-induced CNV and anti-SPARC d-peptide had no effect. Injection 1day after laser injury did not affect size of laser-induced CNV. Inhibition of SPARC activity could be complementary to existing anti-CNV therapy.
Uehara
Hironori
H
John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, 65 Mario Capecchi Dr., Salt Lake City, UT 84132, USA. Hironori.Uehara@hsc.utah.edu
Luo
Ling
L
Simonis
Jacquelyn
J
Singh
Nirbhai
N
Taylor
Ethan Will
EW
Ambati
Balamurali K
BK
D000818:Animals; D020256:Choroidal Neovascularization / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D058449:Intravitreal Injections; D007834:Lasers / Q000009:adverse effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009842:Oligopeptides / Q000378:metabolism*; D015676:Osteonectin / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D010766:Phosphorylation; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism
D009842:Oligopeptides; D015676:Osteonectin; D042442:Vascular Endothelial Growth Factors