An Endostatin-Lentivirus (ES-LV)-EPC Gene Therapy Agent for Suppression of Neovascularization in Oxygen-Induced Retinopathy Rat Models

Abstract Background: Transplantation of gene transfected endothelial progenitor cells (EPCs) has provided novel methods for tumor neovascularization therapy but not for ocular disease therapy. This study aimed to investigate the efficacy of endostatin transfected EPCs in retinal neovascularization therapy. Results: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed the high expression of endostatin in endostatin-lentivirus-EPCs. The neovascularization leakage area and the number of preretinal neovascular cell nuclei were significantly decreased in the endostatin-lentivirus and endostatin-lentivirus-EPC groups, and the effects of these two treatments on inhibiting retinal neovascularization were almost the same. These two groups also showed the greater retinal distribution of endostatin. Intravitreal injections of endostatin-lentivirus-EPCs inhibited retinal neovascularization, vascular endothelial growth factor (VEGF) and CD31 expression, and increased endostatin expression in vivo. Endostatin-lentivirus-EPCs targeted and prevented pathologic retinal neovascularization. Conclusions: Gene-combined EPCs represent a potential new therapeutic agent for the treatment of neovascular eye diseases.

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An Endostatin-Lentivirus (ES-LV)-EPC Gene Therapy Agent for Suppression of Neovascularization in Oxygen-Induced Retinopathy Rat Model

10.21203/rs.2.16501/v2 ◽

2020 ◽

Author(s):

Jing Ai ◽

Jian Ma ◽

Zhi-Qing Chen ◽

Jun-Hui Sun ◽

Ke Yao

Keyword(s):

Retinal Neovascularization ◽

Vascular Endothelial ◽

Cell Nuclei ◽

Oxygen Induced Retinopathy ◽

Disease Therapy ◽

Tumor Neovascularization ◽

Retinal Distribution ◽

Polymerase Chain ◽

Endothelial Growth Factor

Abstract Background: Transplantation of gene transfected endothelial progenitor cells (EPCs) has provided novel methods for tumor neovascularization therapy but not for ocular disease therapy. This study aimed to investigate the efficacy of endostatin transfected EPCs in retinal neovascularization therapy. Results: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed the high expression of endostatin in endostatin-lentivirus-EPCs. The neovascularization leakage area and the number of preretinal neovascular cell nuclei were significantly decreased in the endostatin-lentivirus and endostatin-lentivirus-EPC groups, and the effects of these two treatments on inhibiting retinal neovascularization were almost the same. These two groups also showed the greater retinal distribution of endostatin. Intravitreal injections of endostatin-lentivirus-EPCs inhibited retinal neovascularization, vascular endothelial growth factor (VEGF) and CD31 expression, and increased endostatin expression in vivo. Endostatin-lentivirus-EPCs targeted and prevented pathologic retinal neovascularization. Conclusions: Gene-combined EPCs represent a potential new therapeutic agent for the treatment of neovascular eye diseases.

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Suppression of retinal neovascularization in vivo by inhibition of vascular endothelial growth factor (VEGF) using soluble VEGF-receptor chimeric proteins.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.92.23.10457 ◽

1995 ◽

Vol 92 (23) ◽

pp. 10457-10461 ◽

Cited By ~ 779

Author(s):

L. P. Aiello ◽

E. A. Pierce ◽

E. D. Foley ◽

H. Takagi ◽

H. Chen ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Retinal Neovascularization ◽

Chimeric Proteins ◽

Vegf Receptor ◽

Vascular Endothelial ◽

Endothelial Growth Factor

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A Fairy Chemical Suppresses Retinal Angiogenesis as a HIF Inhibitor

Biomolecules ◽

10.3390/biom10101405 ◽

2020 ◽

Vol 10 (10) ◽

pp. 1405

Author(s):

Deokho Lee ◽

Yukihiro Miwa ◽

Jing Wu ◽

Chiho Shoda ◽

Heonuk Jeong ◽

...

Keyword(s):

Hypoxia Inducible Factor ◽

Inhibitory Effect ◽

Retinal Neovascularization ◽

Vascular Endothelial ◽

Vegf Mrna ◽

Oxygen Induced Retinopathy ◽

Hypoxic Conditions ◽

Chronic Therapy ◽

Retinal Angiogenesis ◽

Endothelial Growth Factor

Neovascular retinal degeneration is a leading cause of blindness in advanced countries. Anti-vascular endothelial growth factor (VEGF) drugs have been used for neovascular retinal diseases; however, anti-VEGF drugs may cause the development of chorioretinal atrophy in chronic therapy as they affect the physiological amount of VEGF needed for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcription factor inducing VEGF expression under hypoxic and other stress conditions. Previously, we demonstrated that HIF was involved with pathological retinal angiogenesis in murine models of oxygen-induced retinopathy (OIR), and pharmacological HIF inhibition prevented retinal neovascularization by reducing an ectopic amount of VEGF. Along with this, we attempted to find novel effective HIF inhibitors. Compounds originally isolated from mushroom-forming fungi were screened for prospective HIF inhibitors utilizing cell lines of 3T3, ARPE-19 and 661W. A murine OIR model was used to examine the anti-angiogenic effects of the compounds. As a result, 2-azahypoxanthine (AHX) showed an inhibitory effect on HIF activation and suppressed Vegf mRNA upregulation under CoCl2-induced pseudo-hypoxic conditions. Oral administration of AHX significantly suppressed retinal neovascular tufts in the OIR model. These data suggest that AHX could be a promising anti-angiogenic agent in retinal neovascularization by inhibiting HIF activation.

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