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

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.

• Authors: Ling Zhang, Xi Shen, Qing Lu, Qingwei Zhou, Jiaqi Gu, Renbao Gan, Hui Zhang, Xiaodong Sun, Bing Xie
• Journal: Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie (Graefes Arch Clin Exp Ophthalmol) Vol. 250 Issue 5 Pg. 731-9 (May 2012) ISSN: 1435-702X [Electronic] Germany
• PMID: 21881847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Angiogenesis Inhibitors
• Collagen Type VIII
• Endostatins
• Peptide Fragments
• Recombinant Proteins
• Vascular Endothelial Growth Factor A
• rhEDI-8t protein, human
• vascular endothelial growth factor A, mouse
• Fibroblast Growth Factor 2

Topics

• Angiogenesis Inhibitors (administration & dosage, therapeutic use)
• Animals
• Cell Line
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Choroidal Neovascularization (pathology, prevention & control)
• Collagen Type VIII (administration & dosage, therapeutic use)
• Disease Models, Animal
• Endostatins (therapeutic use)
• Endothelium, Vascular (cytology, drug effects)
• Female
• Fibroblast Growth Factor 2 (pharmacology)
• Fluorescent Antibody Technique, Indirect
• Humans
• Intravitreal Injections
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Peptide Fragments (administration & dosage, therapeutic use)
• Recombinant Proteins
• Retinal Neovascularization (pathology, prevention & control)
• Specific Pathogen-Free Organisms
• Umbilical Veins (cytology)
• Vascular Endothelial Growth Factor A (genetics, pharmacology)