Hypoxia specific SDF-1 expression by retinal pigment epithelium initiates bone marrow-derived cells to participate in choroidal neovascularization in a laser-induced mouse model

Zhao Xia Zhang, Yu Sheng Wang, Yuan Yuan Shi, Hui Yuan Hou, Chu Zhang, Yan Cai, Guo Rui Dou, Li Bo Yao, Fu Yang Li

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss in patients with age-related macular degeneration (AMD). Stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) plays a critical role in homing of bone marrow-derived cells (BMCs) to choroidal neovascularization (CNV). In this study, we investigated the contribution of hypoxia specific HIF-1α-induced SDF-1 expression in retinal pigment epithelium (RPE) cells and the potential role of SDF-1 in CNV formation. Materials and Methods: Green fluorescent protein (GFP) chimeric mice were developed by transplanting bone marrow cells of gfp +/+ transgenic mice to sublethally irradiated C57BL/6J mice. CNV was induced by laser photocoagulation. Ocular tissue was processed for immunofluorescence to detect HIF-1α and SDF-1 expression, and cell surface markers such as CXCR4, CD34 and CD31 and so on during CNV formation. In vitro, adult human RPE (hRPE) cells were cultured under conditions of chemical hypoxia using CoCl2 administration. And RNAi technique was used to knock down HIF-1α gene to observe the expression of HIF-1α and SDF-1 in hRPE cells. Results: BMCs trafficked around laser lesion adjacent to RPE layer 4h after laser photocoagulation, where SDF-1 expression was relatively higher. With increasing expression of SDF-1, more BMCs were infiltrated into laser lesion to participate in CNV, and both reached peak at 3 d (p<0.05). About 81% BMCs involved in CNV were CXCR4 +. Many of them acquired the surface marker of endothelial precursor cells (CD34 +) and endothelial cells (CD31 +). The constituent ratio of CD34 + and CD31 + BMCs increased with SDF-1 expression. In vitro, we proved that hypoxia specific-HIF-1α influenced SDF-1 expression in hRPE cells. Conclusions: These findings suggested that hypoxia-induced SDF-1 expression in RPE might be a critical initiator for recruitment of BMCs in CNV. SDF-1 might be another important factor in BMCs' differentiation into endothelial cells to participate in the CNV.

Original languageEnglish (US)
Pages (from-to)838-849
Number of pages12
JournalCurrent Eye Research
Volume36
Issue number9
DOIs
StatePublished - Sep 2011
Externally publishedYes

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Chemokine CXCL12
Choroidal Neovascularization
Retinal Pigment Epithelium
Bone Marrow Cells
Lasers
CXCR4 Receptors
Endothelial Cells
Light Coagulation
Hypoxia
Macular Degeneration
RNA Interference
Green Fluorescent Proteins
Inbred C57BL Mouse
Transgenic Mice
Fluorescent Antibody Technique
Cell Differentiation
Cultured Cells

Keywords

  • Bone marrow-derived cells
  • Choroidal neovascularization
  • Hypoxia
  • Hypoxia-inducible factor-1α
  • Stromal cell-derived factor-1

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Hypoxia specific SDF-1 expression by retinal pigment epithelium initiates bone marrow-derived cells to participate in choroidal neovascularization in a laser-induced mouse model. / Zhang, Zhao Xia; Wang, Yu Sheng; Shi, Yuan Yuan; Hou, Hui Yuan; Zhang, Chu; Cai, Yan; Dou, Guo Rui; Yao, Li Bo; Li, Fu Yang.

In: Current Eye Research, Vol. 36, No. 9, 09.2011, p. 838-849.

Research output: Contribution to journalArticle

Zhang, Zhao Xia ; Wang, Yu Sheng ; Shi, Yuan Yuan ; Hou, Hui Yuan ; Zhang, Chu ; Cai, Yan ; Dou, Guo Rui ; Yao, Li Bo ; Li, Fu Yang. / Hypoxia specific SDF-1 expression by retinal pigment epithelium initiates bone marrow-derived cells to participate in choroidal neovascularization in a laser-induced mouse model. In: Current Eye Research. 2011 ; Vol. 36, No. 9. pp. 838-849.
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AU - Zhang, Zhao Xia

AU - Wang, Yu Sheng

AU - Shi, Yuan Yuan

AU - Hou, Hui Yuan

AU - Zhang, Chu

AU - Cai, Yan

AU - Dou, Guo Rui

AU - Yao, Li Bo

AU - Li, Fu Yang

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N2 - Purpose: Choroidal neovascularization (CNV) is a major cause of vision loss in patients with age-related macular degeneration (AMD). Stromal cell-derived factor-1 (SDF-1)/CXC chemokine receptor 4 (CXCR4) plays a critical role in homing of bone marrow-derived cells (BMCs) to choroidal neovascularization (CNV). In this study, we investigated the contribution of hypoxia specific HIF-1α-induced SDF-1 expression in retinal pigment epithelium (RPE) cells and the potential role of SDF-1 in CNV formation. Materials and Methods: Green fluorescent protein (GFP) chimeric mice were developed by transplanting bone marrow cells of gfp +/+ transgenic mice to sublethally irradiated C57BL/6J mice. CNV was induced by laser photocoagulation. Ocular tissue was processed for immunofluorescence to detect HIF-1α and SDF-1 expression, and cell surface markers such as CXCR4, CD34 and CD31 and so on during CNV formation. In vitro, adult human RPE (hRPE) cells were cultured under conditions of chemical hypoxia using CoCl2 administration. And RNAi technique was used to knock down HIF-1α gene to observe the expression of HIF-1α and SDF-1 in hRPE cells. Results: BMCs trafficked around laser lesion adjacent to RPE layer 4h after laser photocoagulation, where SDF-1 expression was relatively higher. With increasing expression of SDF-1, more BMCs were infiltrated into laser lesion to participate in CNV, and both reached peak at 3 d (p<0.05). About 81% BMCs involved in CNV were CXCR4 +. Many of them acquired the surface marker of endothelial precursor cells (CD34 +) and endothelial cells (CD31 +). The constituent ratio of CD34 + and CD31 + BMCs increased with SDF-1 expression. In vitro, we proved that hypoxia specific-HIF-1α influenced SDF-1 expression in hRPE cells. Conclusions: These findings suggested that hypoxia-induced SDF-1 expression in RPE might be a critical initiator for recruitment of BMCs in CNV. SDF-1 might be another important factor in BMCs' differentiation into endothelial cells to participate in the CNV.

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