The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic

O'Leary, O. E. et al. (2019) The vasoreparative potential of endothelial colony-forming cells in the ischemic retina is enhanced by cibinetide, a non-hematopoietic erythropoietin mimetic. Experimental Eye Research, 182, pp. 144-155. (doi:10.1016/j.exer.2019.03.001) (PMID:30876881)

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Abstract

Purpose: Retinal ischemia remains a common sight threatening end-point in blinding diseases such as diabetic retinopathy and retinopathy of prematurity. Endothelial colony forming cells (ECFCs) represent a subpopulation of endothelial progenitors with therapeutic utility for promoting reparative angiogenesis in the ischaemic retina. The current study has investigated the potential of enhancing this cell therapy approach by the dampening of the pro-inflammatory milieu typical of ischemic retina. Based on recent findings that ARA290 (cibinetide), a peptide based on the Helix-B domain of erythropoietin (EPO), is anti-inflammatory and tissue-protective, the effect of this peptide on ECFC-mediated vascular regeneration was studied in the ischemic retina. Methods: The effects of ARA290 on pro-survival signaling and function were assessed in ECFC cultures in vitro. Efficacy of ECFC transplantation therapy to promote retinal vascular repair in the presence and absence of ARA290 was studied in the oxygen induced retinopathy (OIR) model of retinal ischemia. The inflammatory cytokine profile and microglial activation were studied as readouts of inflammation. Results: ARA290 activated pro-survival signaling and enhanced cell viability in response to H2O2-mediated oxidative stress in ECFCs in vitro. Preconditioning of ECFCs with EPO or ARA290 prior to delivery to the ischemic retina did not enhance vasoreparative function. ARA290 delivered systemically to OIR mice reduced pro-inflammatory expression of IL-1β and TNF-α in the mouse retina. Following intravitreal transplantation, ECFCs incorporated into the damaged retinal vasculature and significantly reduced avascular area. The vasoreparative function of ECFCs was enhanced in the presence of ARA290 but not EPO.

Item Type:Articles
Additional Information:This research was supported by grants from Diabetes UK, Fight for Sight (UK), Medical Research Council, Dept for the Economy (NI)/Science Foundation Ireland (SFI), and The Sir Jules Thorn Trust.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Reid, Dr Emma
Authors: O'Leary, O. E., Canning, P., Reid, E., Bertelli, P. M., McKeown, S., Brines, M., Cerami, A., Du, X., Xu, H., Chen, M., Dutton, L., Brazil, D. P., Medina, R. J., and Stitt, A. W.
College/School:College of Medical Veterinary and Life Sciences > School of Life Sciences
Journal Name:Experimental Eye Research
Publisher:Elsevier
ISSN:0014-4835
ISSN (Online):0014-4835
Published Online:12 March 2019

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