December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
Angiogenic Inhibitor K5 Inhibits Retinal Neovascularization Possibly through Down-regulation of VEGF and Up-regulation of PEDF
Author Affiliations & Notes
  • J-X Ma
    Ophthalmology Medical University of South Carolina Charleston SC
  • G Gao
    Ophthalmology Medical University of South Carolina Charleston SC
  • Y Li
    Ophthalmology Medical University of South Carolina Charleston SC
  • S Gee
    Ophthalmology Medical University of South Carolina Charleston SC
  • J Fant
    Ophthalmology Medical University of South Carolina Charleston SC
  • CE Crosson
    Ophthalmology Medical University of South Carolina Charleston SC
  • A Dudley
    Ophthalmology Medical University of South Carolina Charleston SC
  • Footnotes
    Commercial Relationships   J. Ma, None; G. Gao, None; Y. Li, None; S. Gee, None; J. Fant, None; C.E. Crosson, None; A. Dudley, None. Grant Identification: Support: NIH EY12600, EY12231 and EY09741, ADA, JDF and RPE
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 1279. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      J-X Ma, G Gao, Y Li, S Gee, J Fant, CE Crosson, A Dudley; Angiogenic Inhibitor K5 Inhibits Retinal Neovascularization Possibly through Down-regulation of VEGF and Up-regulation of PEDF . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1279.

      Download citation file:


      © ARVO (1962-2015); The Authors (2016-present)

      ×
  • Supplements
Abstract

Abstract: : Purpose:We have previously shown that intravitreal injection of plasminogen kringle 5 (K5), a potent angiogenic inhibitor, inhibits ischemia-induced retinal neovascularization in a rat model. This study was designed to determine the effect of K5 on the regulation of angiogenic homeostasis. Methods:Primary human retinal capillary endothelial cells (HRCEC) and pericytes were isolated, cultured and characterized from donor eyes. Retinal neovascularization was induced in Brown Norway rats by exposure to hyperoxia followed by normoxia. Changes in vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) were determined by Western and Northern blot analyses. HIF-1α nuclear translocation was evaluated by measuring the nuclear levels of HIF-1α. MAP kinase activation was determined by comparison of its phosphorylation level to total MAP kinase. Results:K5 down-regulated an endogenous angiogenic stimulator, VEGF, and up-regulated an angiogenic inhibitor, PEDF, in a dose-dependent manner in primary vascular cells and in rat retinas. Changes in VEGF and PEDF expression by K5 in the retina were correlated with its anti-angiogenic activity in a rat model of ischemia-induced retinopathy. Retinal RNA levels of VEGF and PEDF were also changed by K5. K5 inhibited bFGF-induced p42/p44 MAP kinase activation and ischemia-induced nuclear translocation of HIF-1α. Conclusion:Down-regulation of endogenous angiogenic stimulators and up-regulation of endogenous angiogenic inhibitors, thus leading toward restoration of the balance in angiogenic control, may represent a mechanism for the anti-angiogenic activity of K5. The decreased activation of HIF-1 and p42/p44 MAP kinase may be responsible for the down-regulation of VEGF expression by K5.

Keywords: 566 retinal neovascularization • 388 diabetic retinopathy • 423 growth factors/growth factor receptors 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×