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A potential therapeutic strategy for inhibition of ocular neovascularization with a new endogenous protein: rhEDI-8t

  • Medical Ophthalmology
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Background

Endogenous angiogenesis inhibitors act as natural negative feedback in the focal area during the neovascularization process, and have less interference on physiological angiogenesis, and thus fewer negative side-effects. These inhibitors are potential candidates to combine with or substitutes for current popular anti-angiogenesis treatments to have synergistic effect. In this study, the effects of recombinant endothelial growth inhibitor protein (rhEDI-8t), a novel endogenous protein originated from collagen VIII, was investigated on ocular neovascularization (NV). Endostatin, a well-identified endogenous angiogenesis inhibitor, was compared in parallel and served as a positive control.

Methods

The inhibitory effect of rhEDI-8t on vascular endothelial cells was evaluated by a human umbilical vascular endothelial cells (HUVEC) proliferation test and a bovine aortic endothelial cells (BAEC) migration experiment. The effect of rhEDI-8t on ocular NV was further investigated in mice with choroidal neovascularization (choroidal NV) induced by laser, ischemic retinopathy and transgenic mice with expression of VEGF in photoreceptors (rho/VEGF) respectively.

Results

RhEDI-8t inhibited the growth of HUVECs and migration of BAECs stimulated by basic fibroblast growth factor (bFGF). Mice intravitreally treated with rhEDI-8t showed a significant reduction of choroidal NV, retinal NV and subretinal NV.

Conclusion

Endogenous angiogenesis inhibitor rhEDI-8t showed a potent anti-angiogenesis effect in both in vitro and in vivo experiments. It contributed to the suppression of ocular NV. The study suggested that rhEDI-8t could be a subsidiary potent therapeutic medicine in addition to anti-VEGF therapy in future clinical anti-angiogenesis treatment.

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Abbreviations

NV:

Neovascularization

VEGF:

Vascular endothelial growth factor

rho/VEGF:

Rhodopsin promoter/ VEGF

AMD:

Age-related macular degeneration

HUVEC:

Human umbilical vascular endothelial cells

BAEC:

Bovine aortic endothelial cells

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Acknowledgments

Supported by Shanghai Leading Academic Discipline Project S30205, Shanghai Municipal Education Committee Project 09YZ86, Shanghai Rising-Star Program 10QA1404600, Shanghai Nature Science Foundation 11ZR1422000, China.

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Authors and Affiliations

  1. The Department of Ophthalmology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197, Ruijin Er Road, Shanghai, China, 200025

    Ling Zhang, Xi Shen, Qing Lu, Jiaqi Gu & Bing Xie

  2. The Department of Ophthalmology, Shanghai First People’s Hospital, Shanghai Jiao Tong University, 100, Haining Road, Shanghai, China, 200080

    Ling Zhang & Xiaodong Sun

  3. Shanghai Apeloa Pharmaceutical Research Institute, 1399 Yuanzhong Road, Nanhui, Shanghai, China, 201314

    Qingwei Zhou, Renbao Gan & Hui Zhang

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  1. Ling Zhang
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  2. Xi Shen
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  3. Qing Lu
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  9. Bing Xie
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Corresponding authors

Correspondence to Xiaodong Sun or Bing Xie.

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Ling Zhang and Xi Shen contributed equally to the manuscript

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Zhang, L., Shen, X., Lu, Q. et al. A potential therapeutic strategy for inhibition of ocular neovascularization with a new endogenous protein: rhEDI-8t. Graefes Arch Clin Exp Ophthalmol 250, 731–739 (2012). https://doi.org/10.1007/s00417-011-1765-y

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  • DOI: https://doi.org/10.1007/s00417-011-1765-y

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