Endothelial progenitor dysfunction in the pathogenesis of diabetic retinopathy: treatment concept to correct diabetes-associated deficits

Abstract

Progressive obliteration of the retinal microvessels is a characteristic of diabetic retinopathy and the resultant retinal ischemia can lead to sight-threatening macular edema, macular ischemia and ultimately preretinal neovascularization. Bone marrow derived endothelial progenitor cells (EPCs) play a critical role in vascular maintenance and repair. There is still great debate about the most appropriate markers that define an EPC. EPCs can be isolated using cell sorting by surface phenotype selection or in vitro cell culture. For freshly isolated cells, EPC cell sorting is heavily dependent on the surface markers used; EPCs can also be isolated by in vitro propagation of heterogeneous mixtures of cells in culture using adhesion to specific substrates and cell growth characteristics. in vitro isolation enables consistent reproducibility and using this approach at least two distinct types of EPCs with different angiogenic properties have been identified from adult peripheral and umbilical cord blood; early EPCs (eEPCs) and late outgrowth endothelial progenitor cells (OECs). Emerging studies demonstrate the potential of these cells in revascularization of ischemic/injured retina in animal models of retinal disease. Since ischemic retinopathies are leading causes of blindness, they are a potential disease target for EPC-based therapy. In this chapter, we summarize the current knowledge about EPCs and discuss the possibility of cellular therapy for treatment of diabetic macular ischemia and the vasodegenerative phase of diabetic retinopathy. We also report current pharmacological options that can be utilized to correct diabetes associated defects in EPCs so as to enhance the therapeutic utility of these cells.