1. Lentivirus-mediated sFlt-1 gene fragment transfer suppresses retinal neovascularization.
- Author
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Min Z, Qiang W, Benwen S, Bin L, and Xinhua D
- Subjects
- Animals, Animals, Newborn, Blotting, Western, Fluorescein Angiography, Immunohistochemistry, Ischemia chemically induced, Ischemia complications, Mice, Oxygen, Retinal Neovascularization diagnosis, Retinal Neovascularization etiology, Retinal Neovascularization metabolism, Retinal Vessels, Vascular Endothelial Growth Factor A metabolism, Vascular Endothelial Growth Factor Receptor-2 antagonists & inhibitors, Gene Transfer Techniques, Genetic Vectors, Lentivirus genetics, Peptide Fragments genetics, Retinal Neovascularization therapy, Vascular Endothelial Growth Factor Receptor-2 genetics
- Abstract
Purpose: sFlt-1, a soluble secreted variant of the vascular endothelial growth factor (VEGF) receptor-1 that possesses only its extracellular domain, is a specific endogenous inhibitor of VEGF, which is involved in retinal vasculogenesis. Our objective was to determine the effects of various sFlt-1 gene fragments on retinal neovascularization in vivo using a murine oxygen-induced ischemic retinopathy (OIR) model., Methods: Lentiviral expression plasmids carrying the sFlt-1 gene fragments containing Ig-like domains 2nd-3rd and 2nd-4th were constructed. Retinal neovascularization was induced by exposing neonatal mice to hyperoxia (75% O(2)) on post-natal day 7 (P7) and then returning them to normoxia (21% O(2)) on P12. After sFlt-1 gene fragment transfer, retinal neovascularization was examined via fluorescein angiography and hematoxylin-eosin staining. In addition, changes in the expression of VEGF and its functional receptor KDR/Flk-1 were examined via Western blotting and immunohistochemistry., Results: Lenti.sFlt-1(2-3) and lenti.sFlt-1(2-4) both significantly inhibited neovascularization in OIR mice. Retinas from mice treated with lenti.sFlt-1(2-3) demonstrated a more marked reduction in neovascular cell nuclei compared with mice treated with lenti.sFlt-1(2-4), and these results were confirmed by fluorescence angiography. Gene transfer showed a very weak effect on VEGF protein expression, whereas KDR/Flk-1 protein expression was strongly inhibited, particularly in mice treated with lenti.sFlt-1(2-3)., Conclusions: Lentivirus-mediated sFlt-1 gene transfer significantly inhibits retinal neovascularization in OIR. Thus, sFlt-1 gene transfer may represent a potential therapeutic strategy for preventing retinal neovascularization.
- Published
- 2009
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