Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy

Xialin Liu, Yongjun Li, Yizhi Liu, Yan Luo, Dingding Wang, Brian H. Annex, Pascal Goldschmidt-Clermont

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors.

Original languageEnglish
Pages (from-to)504-515
Number of pages12
JournalAmerican Journal of Pathology
Volume176
Issue number1
DOIs
StatePublished - Jan 1 2010

Fingerprint

Pathologic Neovascularization
Nerve Growth Factors
Diabetic Retinopathy
Retinal Neovascularization
Endothelial Progenitor Cells
Brain-Derived Neurotrophic Factor
Nerve Growth Factor
Diabetes Complications
Hindlimb
Blood Vessels
Retina
Intercellular Signaling Peptides and Proteins
Flow Cytometry
Stem Cells
Ischemia
Enzyme-Linked Immunosorbent Assay

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy. / Liu, Xialin; Li, Yongjun; Liu, Yizhi; Luo, Yan; Wang, Dingding; Annex, Brian H.; Goldschmidt-Clermont, Pascal.

In: American Journal of Pathology, Vol. 176, No. 1, 01.01.2010, p. 504-515.

Research output: Contribution to journalArticle

Liu, Xialin ; Li, Yongjun ; Liu, Yizhi ; Luo, Yan ; Wang, Dingding ; Annex, Brian H. ; Goldschmidt-Clermont, Pascal. / Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy. In: American Journal of Pathology. 2010 ; Vol. 176, No. 1. pp. 504-515.
@article{db4a232902fd44629869fe6a018f864b,
title = "Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy",
abstract = "Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors.",
author = "Xialin Liu and Yongjun Li and Yizhi Liu and Yan Luo and Dingding Wang and Annex, {Brian H.} and Pascal Goldschmidt-Clermont",
year = "2010",
month = "1",
day = "1",
doi = "10.2353/ajpath.2010.081152",
language = "English",
volume = "176",
pages = "504--515",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Endothelial progenitor cells (EPCs) mobilized and activated by neurotrophic factors may contribute to pathologic neovascularization in diabetic retinopathy

AU - Liu, Xialin

AU - Li, Yongjun

AU - Liu, Yizhi

AU - Luo, Yan

AU - Wang, Dingding

AU - Annex, Brian H.

AU - Goldschmidt-Clermont, Pascal

PY - 2010/1/1

Y1 - 2010/1/1

N2 - Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors.

AB - Diabetic retinopathy is characterized by pathological retinal neovascularization. Accumulating evidence has indicated that high levels of circulating endothelial progenitor cells (EPCs) are an important risk factor for neovascularization. Paradoxically, the reduction and dysfunction of circulating EPCs has been extensively reported in diabetic patients. We hypothesized that EPCs are differentially altered in the various vasculopathic complications of diabetes mellitus, exhibiting distinct behaviors in terms of angiogenic response to ischemia and growth factors and potentially playing a potent role in motivating vascular precursors to induce pathological neovascularization. Circulating levels of EPCs from diabetic retinopathy patients were analyzed by flow cytometry and by counting EPC colony-forming units, and serum levels of neurotrophic factors were measured by enzyme-linked immunosorbent assay. We found increased levels of nerve growth factor and brain-derived neurotrophic factor in the blood of diabetic retinopathy patients; this increase was correlated with the levels of circulating EPCs. In addition, we demonstrated that retinal cells released neurotrophic factors under hypoxic conditions to enhance EPC activity in vitro and to increase angiogenesis in a mouse ischemic hindlimb model. These results suggest that neurotrophic factors may induce neoangiogenesis through EPC activation, leading to the pathological retinal neovascularization. Thus, we propose that neovascularization in the ischemic retina might be regulated by overexpression of neurotrophic factors.

UR - http://www.scopus.com/inward/record.url?scp=73949132075&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73949132075&partnerID=8YFLogxK

U2 - 10.2353/ajpath.2010.081152

DO - 10.2353/ajpath.2010.081152

M3 - Article

VL - 176

SP - 504

EP - 515

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 1

ER -