Intraocular Gutless Adenoviral-Vectored VEGF Stimulates Anterior Segment but not Retinal Neovascularization

Yuji Oshima, Kyoichi Takahashi, Sachiko Oshima, Yoshitsugu Saishin, Yumiko Saishin, Raquel Lima Silva, Xaoling Liang, P. Seshidhar Reddy, Shanthi Ganesh, Terrence Brann, Gene Liau, Michael Kaleko, Sheila Connelly, Peter A. Campochiaro

Research output: Contribution to journalArticle

Abstract

Vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) have been implicated as important stimulatory factors for retinal neovascularization. In this study, we used intraocular gene transfer with gutless adenoviral (AGV) vectors to determine the effect of increased intraocular expression of VEGF, IGF-1, or sphingosine kinase (SPK), which produces sphingosine-1-phosphate, another angiogenic factor. Retinal neovascularization did not occur from intravitreous AGV-vectored VEGF, IGF-1, SPK, or combined VEGF and IGF-1, except occasionally adjacent to the retinal penetration site from the injection. However, corneal and iris neovascularization occurred after 2 weeks in all eyes injected with AGV.VEGF, but not those injected with only AGV.IGF-1 or AGV.SPK. These data suggest that the superficial capillary bed of the retina is relatively insensitive to VEGF, IGF-1, or SPK in adult mice, except when combined with retinal trauma. However, AGV-vectored VEGF is sufficient to consistently cause severe corneal and iris neovascularization. This provides a model for anterior segment neovascularization, which unlike previous models is relatively inexpensive and is not plagued by spontaneous regression, and therefore, may be useful for identification of new treatments.

Original languageEnglish (US)
Pages (from-to)399-411
Number of pages13
JournalJournal of Cellular Physiology
Volume199
Issue number3
DOIs
StatePublished - Jun 1 2004

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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    Oshima, Y., Takahashi, K., Oshima, S., Saishin, Y., Saishin, Y., Lima Silva, R., Liang, X., Reddy, P. S., Ganesh, S., Brann, T., Liau, G., Kaleko, M., Connelly, S., & Campochiaro, P. A. (2004). Intraocular Gutless Adenoviral-Vectored VEGF Stimulates Anterior Segment but not Retinal Neovascularization. Journal of Cellular Physiology, 199(3), 399-411. https://doi.org/10.1002/jcp.10441