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Correction of Diabetes-Induced Endothelial Progenitor Dysfunction to Promote Retinal Vascular Repair

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New Strategies to Advance Pre/Diabetes Care: Integrative Approach by PPPM

Part of the book series: Advances in Predictive, Preventive and Personalised Medicine ((APPPM,volume 3))

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Abstract

Progressive obliteration of the retinal microvessels is a characteristic of diabetic retinopathy and the resultant retinal ischemia that 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 and much deliberation occurs regarding the plasticity of monocytes and their ability to promote repair as well as contribute to angiogenesis. EPC populations 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; EPC populations 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 with this approach at least two distinct types of populations with different angiogenic properties have been identified from adult peripheral and umbilical cord blood. These groups are early EPCs (eEPCs) and “endothelial colony forming cells” (ECFCs), initially termed “late outgrowth endothelial progenitor cells” (OECs).

Emerging studies demonstrate the potential of these cells in revascularization of ischemic/injured tissues including the retina. Since ischemic retinopathies are the leading causes of blindness, they are a potential disease target for cell based therapy. In this chapter, we summarize the current knowledge about the most well described EPC populations and discuss the possibility of cell therapy for treatment of diabetic macular ischemia and the vasodegenerative phase of diabetic retinopathy. We also report on current pharmacological options that can be utilized to correct diabetes associated defects in one particular EPC population, CD34+ cells, so that these cells can potentially be used therapeutically.

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Acknowledgements

This work was supported by grants from the National Institutes of Health (NIH1R01 EY07739, NIH R01EY12601), American Heart Association (Beginning Grant-in-Aid # 0865213E to S. L.C.) and the Juvenile Diabetes Research Foundation (Grant 4-2000-847).

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  1. Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, 1600 SW Archer Road, Gainesville, FL, 32610, USA

    Sergio Li Calzi, Matthew Neu, Lynn C. Shaw & Maria B. Grant

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  1. Sergio Li Calzi
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Correspondence to Maria B. Grant .

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  1. Dental Medicine, Oral Biology Faculty, Georgia Regents University, Laney Walker Blvd. 1459, Augusta, 30912, Georgia, USA

    Mahmood S. Mozaffari

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Calzi, S.L., Neu, M., Shaw, L.C., Grant, M.B. (2013). Correction of Diabetes-Induced Endothelial Progenitor Dysfunction to Promote Retinal Vascular Repair. In: Mozaffari, M. (eds) New Strategies to Advance Pre/Diabetes Care: Integrative Approach by PPPM. Advances in Predictive, Preventive and Personalised Medicine, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5971-8_6

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