Abstract
Abstract: :
Purpose: We have recently reported that fragments of tryptophanyl-tRNA synthetase (T2) are potent anti-angiogenics. We have also shown that endothelial progenitor cells localize to, and become part of, newly forming murine retinal vasculature. This study utilizes cell-based delivery of T2 to inhibit angiogenesis in a murine retinal model. Methods: MACS was used to separate Lin- progenitor cells from murine bone marrow. Cells were transfected with a plasmid encoding an IgΚ chain signal sequence and T2. Transfected cells were injected intravitreally into postnatal day 3 murine eyes. Eyes were harvested nine days later and were stained with Collagen IV antibody to analyze the effect on the developing vascular network. Results: Western blot analysis confirmed the production of secreted T2 by transfected endothelial progenitor cells. Eyes receiving T2 transfected endothelial progenitor cells exhibited complete disruption of ongoing retinal angiogenesis. Injection of cells transfected with control plasmid, had no effect on angiogenesis. Conclusion: These results demonstrate that cell-based delivery can be used to selectively target neovascularization in the eye with novel, potent anti-angiogenics.
Keywords: 483 neovascularization • 566 retinal neovascularization