, Volume 2, Issue 1, pp 93–104 | Cite as

Lipid hydroperoxide stimulates retinal neovascularization in rabbit retina through expression of tumor necrosis factor-a, vascular endothelial growth factor and platelet-derived growth factor

  • Donald Armstrong
  • Toshihiko Ueda
  • Takako Ueda
  • Ahmad Aljada
  • Richard Browne
  • Shohei Fukuda
  • Robert Spengler
  • Richard Chou
  • Mary Hartnett
  • Peter Buch
  • Paresh Dandona
  • Ram Sasisekharan
  • C. Kathleen Dorey


To test the hypothesis that oxidative damage associated with tissue hypoxia plays a role in neovascularization, a lipid hydroperoxide (LHP) was injected into the vitreous of rabbits. Single injections of LHP (50–600μg) caused a sustained retinal neovascularization visualized clinically by ophthalmoscopy and confirmed by microscopy. Vasodilators, i.e. histamine and nitric oxide, peaked at 6h and 7 days, respectively. The levels of both tumor necrosis factor-α and interleukin-lα peaked at 12h and dropped to basal levels by 24h. Expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β peaked at 24h and were sustained throughout the following 3 weeks, and platelet-derived growth factor was also elevated throughout the same period. Upregulation of these five angiogenic cytokines, but not basic fibroblast growth factor, occurred prior to the appearance of neovascularization. Leakage of fluorescein at the tips of new vessels was demonstrated by fluorescein angiography. Linoleic hydroperoxide induced neovascularization, but saturated or unsaturated native C-18 fatty acids had no effect. The cascade of multiple, angiogenic cytokines induced by LHP may interact to promote sustained neovascularization.

Lipid hydroperoxidase neovascularization platelet-derived growth factor tumor necrosis factor-α vascular endothelial growth factor 


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Copyright information

© Chapman and Hall 1998

Authors and Affiliations

  • Donald Armstrong
    • 1
  • Toshihiko Ueda
    • 1
  • Takako Ueda
    • 1
  • Ahmad Aljada
    • 1
  • Richard Browne
    • 1
  • Shohei Fukuda
    • 1
  • Robert Spengler
    • 2
  • Richard Chou
    • 2
  • Mary Hartnett
    • 3
  • Peter Buch
    • 3
  • Paresh Dandona
    • 4
  • Ram Sasisekharan
    • 5
  • C. Kathleen Dorey
    • 6
  1. 1.Department of Clinical Laboratory ScienceState University of New York at BuffaloUSA
  2. 2.Department of PathologyState University of New York at BuffaloUSA
  3. 3.Department of OphthalmologyState University of New York at BuffaloUSA
  4. 4.Department of MedicineState University of New York at BuffaloUSA
  5. 5.Division of Health Sciences and TechnologyHarvard University–Massachusetts Institute of TechnologyCambridgeUSA
  6. 6.Schepens Eye Research InstituteHarvard Medical SchoolBostonUSA

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