Evaluation of Circulating Endothelial Progenitor Cells (EPCs), Circulating Progenitor Cells (CPCs) and Circulating Endothelial Cells (CECs) in AMD Patients

Abstract

Purpose: : To evaluate circulating endothelial and progenitor cells as biomarkers in exudative and atrophic AMD patients, in order to establish the possible clinical usefulness of their assessment.

Methods: : Peripheral venous blood samples from 12 patients with dry AMD and 19 newly diagnosed neovascular AMD were analyzed before and 4 weeks after three intravitreal injections of ranibizumab. At baseline and after treatment the patients underwent standard ophthalmological examination, fluorescein angiography and OCT scan; the wet AMD patients were distinguished in two groups ( responders and non responders ) according to visual acuity and OCT foveal thickness modifications. The number of circulating endothelial progenitor cells (EPCs: CD34+/KDR+; CD133+/KDR+; CD34+/KDR+/CD133+), circulating progenitor cells (CPCs: CD34+; CD133+; CD34+/CD133+) and circulating endothelial cells (CECs) were determined by flow cytometry at baseline in all the patients and after treatment in the wet AMD group. For statistical analysis the Mann-Whitney test was used to compare the average results between the different groups while the Wilcoxon test for unpaired data was used to compare data before and after treatment. SPSS11.5 software was used for statistical analyisis.

Results: : No statistically significant difference for EPCs and CECs was found between patients with dry and wet AMD whereas CPC levels were increased in exudative AMD vs atrophic AMD patients, especially those of the cellular subset CD133+ (p=0.0035 ) . A significant EPC level reduction was observed after treatment (p=0.011 for CD34+/KDR+, p=0.012 for CD133+/KDR+, p=0.038 for CD34+/KDR+/CD133+ ). Finally no significant difference was found between responders and non responders to the antiangiogenic treatment, even if the group with the worst clinical outcome showed a higher number of CPCs at baseline.

Conclusions: : We have reported higher levels of CPCs in exudative than dry AMD and a significant reduction of EPCs after three intravitreal injections of ranibizumab. The level of circulating endothelial and progenitor cells may represent an useful biomarker of choroidal neovascularization and of its response to antiangiogenic treatment.

Keywords: age-related macular degeneration • retina • flow cytometry