Bone marrow derived CX3CR1+ progenitors facilitate vascular repair in a murine model of ischemic retinopathy

Abstract

Purpose : Bone marrow (BM) contains a population of progenitor cells that can differentiate into proangiogenic microglia or macrophages under various ischemic conditions. We previously described a subpopulation of myeloid progenitors that differentiate into microglia that promote vascular repair in the oxygen induced retinopathy (OIR) model. However, it is not clear which stage of differentiation in this lineage regulates retinal vascular repair. The chemokine receptor CX3CR1 has been associated with the monocyte/macrophage/dendritic cell lineage, while CD34 is associated with their progenitor cell(s). In this study, we show that intravitreal injection of undifferentiated CX3CR1+CD34+ BM cells facilitates normalization of the vasculature in OIR.

Methods : BM cells from 6 week old transgenic CX3CR1^gfp/+ reporter mice were isolated by flow cytometry. Wild-type p7 pups were injected with 1 x 10⁵ of GFP+CD34⁺ or GFP+CD34^- cells before undergoing oxygen induced retinopathy (OIR). Flat mount staining for isolectin B4 was performed at P17.

Results : In flow cytometric analysis, 3.1 % of BM cells were CX3CR1+CD34+ and 2.3 % were CX3CR1+CD34-. In the OIR model, injected CX3CR1+CD34+ BM cells homed to the retinal vessels more than CX3CR1+CD34-; and injection of CX3CR1+CD34+ BM cells decreased both the area of vascular obliteration and neovascular tufts compared to CX3CR1+CD34- BM cells (p=0.019 and p=0.018, respectively).

Conclusions : BM-derived CX3CR1+ progenitors potentiate vascular repair in the OIR model. Injection of those cells may provide a therapeutic benefit for the treatment of retinal vascular disease.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.