RC Andrew Symons, Bliss E OÕBryhim

Purpose:
To examine the role of endothelial progeni-tor cells (EPCs) in the mouse model of Retinopathy ofPrematurity, Oxygen Induced Retinopathy (OIR) andtheir potential as a therapeutic target, including thework of the authors and a review of the literature.

Method:
C57BL/6 and tyrosinase null B6(Cg)-Tyrc-2J/J mice were used. Retinopathy was induced at post-natal day seven by exposure of mouse pups to 75%inspired oxygen for up to 120 hours. In differentexperiments, proportions of putative EPCs in the bonemarrow and peripheral blood circulation, numbers ofEPCs present in revascularizing regions of the retinaand the extent of retinal avascular areas were meas-ured using flow cytometry, confocal microscopy andstandard fluorescence microscopy at different timepoints. Dopaminergic modulating drugs and vehiclecontrols were administered intraperitoneally in further experiments.

Results:
A time study showed that EPCs in the bonemarrow, peripheral and retina compartments arehighly dynamic during the hyperoxic and earlyhypoxic phases of OIR. Compared with wild-typemice, tyrosinase null mice were found to have a greater number of EPCs in their bone marrow andperipheral circulation, and to have greater numbers ofEPCs recruited to the retina at P13. This was associatedwith smaller avascular areas. Dopaminergic modula-tion was found to alter recruitment of EPCs to theretina and retinal revascularization rates.

Conclusion:
Endothelial progenitor cells were foundto be a dynamic and modifiable cell population in theOIR model and EPC numbers were associated withretinal revascularization. Other studies have foundthat EPCs and other bone marrow derived angiogeniccells have a role in revascularization of the retina andin pathological neovascularization in the OIR model.Our work has demonstrated that pharmacologicalmanipulation of EPCs can modify retinal revas-cularization in OIR, and others have demonstratedthat introduction of EPCs by intravitreal injection canalso enhance retinal revascularization. Thus, EPCshave become a therapeutic target in OIR, and this mayindicate the potential of EPCs as a therapeutic target inRetinopathy of Prematurity.