Hematopoietic Stem Cell Contribution to Neovascularization of the Iris

Abstract

Abstract: : Purpose: Neovascularization (NV) of the iris is the most severe form of ocular NV and will become more frequent with the gentrification of the population. Iris NV usually occurs secondary to other ocular disorders. We have previously shown hematopoietic stem cell (HSC) involvement in murine models of preretinal and choroidal NV (CNV). In this study, we investigated if HSC also contribute to iris NV. Methods: Lethally irradiated adult C57BL/6J mice were reconstituted with purified Sca–1⁺/Lin^– stem cells from green fluorescent protein (gfp) homozygous donor mice. Transplanted mice were injected with a recombinant adeno–associated viral vector containing the full–length gene for human vascular endothelial growth factor in both the anterior chamber and the vitreous immediately following branch retinal vein occlusion by laser photocoagulation. Animals were euthanized and enucleated at 1, 2 and 3 weeks post injection and laser treatment. The iris and cornea were dissected intact and treated with rhodamine–conjugated R. communis agglutinin to stain vasculature. The iris was then removed from the cornea and examined by confocal microscopy. Results: Cells expressing gfp (thus donor HSC–derived) were observed as soon as 1 week following treatment and persisted throughout the course of the study. Gfp+ cells incorporated into iris NV to a limited degree. Conclusions: While gfp+ cells incorporated into new vessels in this model, their contribution to iris NV appears to be less than that observed in prior studies of preretinal and CNV. Thus, adult stem cells contribute to the formation of iris NV and may provide a limited target for therapies designed to prevent this disorder.

Keywords: iris • neovascularization • pathology: experimental