Uehara Hironori, Luo Ling, Simonis Jacquelyn, Singh Nirbhai, Taylor Ethan Will, Ambati Balamurali K
John A. Moran Eye Center, Department of Ophthalmology and Visual Sciences, University of Utah, 65 Mario Capecchi Dr., Salt Lake City, UT 84132, USA.
Vision Res. 2010 Mar 31;50(7):674-9. doi: 10.1016/j.visres.2009.12.003. Epub 2009 Dec 22.
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.
已知SPARC调控血管内皮生长因子A(VEGF-A)向主要血管生成性VEGF受体激酶插入域受体(KDR)的信号转导。我们试图确定使用抗SPARC肽抑制SPARC活性是否可通过促进VEGF-A与Fms样酪氨酸激酶1(FLT-1)结合来抑制激光诱导的脉络膜新生血管(CNV)。我们制备了抗SPARC l肽和反向抗SPARC d肽。在激光诱导前或后1天经玻璃体腔注射抗SPARC肽或磷酸盐缓冲盐水(PBS)。激光诱导前1天经玻璃体腔注射抗SPARC l肽可促进FLT-1磷酸化并抑制激光诱导的CNV,而抗SPARC d肽则无作用。激光损伤后1天注射对激光诱导的CNV大小无影响。抑制SPARC活性可能是现有抗CNV治疗的补充。