TY - JOUR
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
N1 - Funding Information:
The authors thank the Shanghai Institute of Burns for place and facility assistance. Supported by the National Nature Science Foundation of China Grant No. 82470639 and Grant No. 81570853.
Funding Information:
The authors thank the Shanghai Institute of Burns for place and facility assistance. Supported by the National Nature Science Foundation of China Grant No. 82470639 and Grant No. 81570853. Disclosure: T. Su, None; Y. Zhong, None; A.M. Demetriades, None; J. Shen, None; A. Sui, None; Y. Yao, None; Y. Gao, None; Y. Zhu, None; X. Shen, None; B. Xie, None
Publisher Copyright:
© 2018 The Authors.
PY - 2018/2
Y1 - 2018/2
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.
KW - Endocan
KW - Endothelial cell
KW - Ocular neovascularization
KW - Vascular endothelial growth factor
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U2 - 10.1167/iovs.17-22945
DO - 10.1167/iovs.17-22945
M3 - Article
C2 - 29450540
AN - SCOPUS:85042331216
SN - 0146-0404
VL - 59
SP - 930
EP - 939
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -