Endocan blockade suppresses experimental ocular neovascularization in mice

Ting Su, Yisheng Zhong, Anna M. Demetriades, Jikui Shen, Ailing Sui, Yiyun Yao, Yushuo Gao, Yanji Zhu, Xi Shen, Bing Xie

Research output: Contribution to journalArticle

Abstract

PURPOSE. Ocular neovascularization (NV) is a pathologic process characterized by the proliferation and infiltration of various types of cells such as RPE, glial, and endothelial cells, which interact with proangiogenic factors and inflammatory cytokines. Endocan is known to be enriched in retinal endothelial tip cells under hypoxia, but the effect of endocan on ocular NV progression is largely unknown. In this study, we investigated the role of endocan in the ocular NV pathologic process and the possible mechanisms involved. METHODS. In the eyes of mice with oxygen-induced retinopathy (OIR); choroidal NV (CNV); and rhodopsin promoter (rho)/VEGF transgenic mice, endocan expression was assessed by quantitative real-time PCR (RT-PCR) and Western blot. In vivo, a specific functional antibody was used to neutralize endocan and ocular NV levels were evaluated by RT-PCR, Western blot and immunostaining of flat-mounts. In vitro, the effect of endocan on human retinal microvascular endothelial cell (HREC) tube formation was observed using a routine method. RESULTS. Endocan was significantly elevated in these three experimental mice models. Endocan blockade with the neutralizer intravitreal injection not only suppressed the area of retinal, choroidal and subretinal NV, but also resulted in a decrease in several angiogenesisassociated molecules. Recombinant endocan protein (rhEndocan) was found to induce tube formation on HRECs directly. CONCLUSIONS. The current data suggest that endocan is a potential therapeutic or an additional target for retinal and subretinal NV diseases.

Original languageEnglish (US)
Pages (from-to)930-939
Number of pages10
JournalInvestigative Ophthalmology and Visual Science
Volume59
Issue number2
DOIs
StatePublished - Feb 1 2018

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Choroidal Neovascularization
Endothelial Cells
Pathologic Processes
Real-Time Polymerase Chain Reaction
Western Blotting
Retinal Neovascularization
Cell Hypoxia
Intravitreal Injections
Rhodopsin
Recombinant Proteins
Neuroglia
Vascular Endothelial Growth Factor A
Transgenic Mice
Theoretical Models
Cytokines
Oxygen
Antibodies
Therapeutics
In Vitro Techniques

Keywords

  • Endocan
  • Endothelial cell
  • Ocular neovascularization
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Endocan blockade suppresses experimental ocular neovascularization in mice. / Su, Ting; Zhong, Yisheng; Demetriades, Anna M.; Shen, Jikui; Sui, Ailing; Yao, Yiyun; Gao, Yushuo; Zhu, Yanji; Shen, Xi; Xie, Bing.

In: Investigative Ophthalmology and Visual Science, Vol. 59, No. 2, 01.02.2018, p. 930-939.

Research output: Contribution to journalArticle

Su, T, Zhong, Y, Demetriades, AM, Shen, J, Sui, A, Yao, Y, Gao, Y, Zhu, Y, Shen, X & Xie, B 2018, 'Endocan blockade suppresses experimental ocular neovascularization in mice', Investigative Ophthalmology and Visual Science, vol. 59, no. 2, pp. 930-939. https://doi.org/10.1167/iovs.17-22945
Su, Ting ; Zhong, Yisheng ; Demetriades, Anna M. ; Shen, Jikui ; Sui, Ailing ; Yao, Yiyun ; Gao, Yushuo ; Zhu, Yanji ; Shen, Xi ; Xie, Bing. / Endocan blockade suppresses experimental ocular neovascularization in mice. In: Investigative Ophthalmology and Visual Science. 2018 ; Vol. 59, No. 2. pp. 930-939.
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T1 - Endocan blockade suppresses experimental ocular neovascularization in mice

AU - Su, Ting

AU - Zhong, Yisheng

AU - Demetriades, Anna M.

AU - Shen, Jikui

AU - Sui, Ailing

AU - Yao, Yiyun

AU - Gao, Yushuo

AU - Zhu, Yanji

AU - Shen, Xi

AU - Xie, Bing

PY - 2018/2/1

Y1 - 2018/2/1

N2 - PURPOSE. Ocular neovascularization (NV) is a pathologic process characterized by the proliferation and infiltration of various types of cells such as RPE, glial, and endothelial cells, which interact with proangiogenic factors and inflammatory cytokines. Endocan is known to be enriched in retinal endothelial tip cells under hypoxia, but the effect of endocan on ocular NV progression is largely unknown. In this study, we investigated the role of endocan in the ocular NV pathologic process and the possible mechanisms involved. METHODS. In the eyes of mice with oxygen-induced retinopathy (OIR); choroidal NV (CNV); and rhodopsin promoter (rho)/VEGF transgenic mice, endocan expression was assessed by quantitative real-time PCR (RT-PCR) and Western blot. In vivo, a specific functional antibody was used to neutralize endocan and ocular NV levels were evaluated by RT-PCR, Western blot and immunostaining of flat-mounts. In vitro, the effect of endocan on human retinal microvascular endothelial cell (HREC) tube formation was observed using a routine method. RESULTS. Endocan was significantly elevated in these three experimental mice models. Endocan blockade with the neutralizer intravitreal injection not only suppressed the area of retinal, choroidal and subretinal NV, but also resulted in a decrease in several angiogenesisassociated molecules. Recombinant endocan protein (rhEndocan) was found to induce tube formation on HRECs directly. CONCLUSIONS. The current data suggest that endocan is a potential therapeutic or an additional target for retinal and subretinal NV diseases.

AB - PURPOSE. Ocular neovascularization (NV) is a pathologic process characterized by the proliferation and infiltration of various types of cells such as RPE, glial, and endothelial cells, which interact with proangiogenic factors and inflammatory cytokines. Endocan is known to be enriched in retinal endothelial tip cells under hypoxia, but the effect of endocan on ocular NV progression is largely unknown. In this study, we investigated the role of endocan in the ocular NV pathologic process and the possible mechanisms involved. METHODS. In the eyes of mice with oxygen-induced retinopathy (OIR); choroidal NV (CNV); and rhodopsin promoter (rho)/VEGF transgenic mice, endocan expression was assessed by quantitative real-time PCR (RT-PCR) and Western blot. In vivo, a specific functional antibody was used to neutralize endocan and ocular NV levels were evaluated by RT-PCR, Western blot and immunostaining of flat-mounts. In vitro, the effect of endocan on human retinal microvascular endothelial cell (HREC) tube formation was observed using a routine method. RESULTS. Endocan was significantly elevated in these three experimental mice models. Endocan blockade with the neutralizer intravitreal injection not only suppressed the area of retinal, choroidal and subretinal NV, but also resulted in a decrease in several angiogenesisassociated molecules. Recombinant endocan protein (rhEndocan) was found to induce tube formation on HRECs directly. CONCLUSIONS. The current data suggest that endocan is a potential therapeutic or an additional target for retinal and subretinal NV diseases.

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