Tat PTD-Endostatin-RGD: A novel protein with anti-angiogenesis effect in retina via eye drops

Yan Li, Lian Li, Zhiwei Li, Juzheng Sheng, Xinke Zhang, Danyang Feng, Xu Zhang, Fengxin Yin, Aijun Wang, Fengshan Wang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background Diabetic retinopathy is a leading cause of blindness. The objective was to design a novel fusion protein, Tat PTD-Endostatin-RGD, to treat retinal neovascularization via eye drops instead of traditional intravitreal injection trepapeutical methods. Method The anti-angiogenesis ability was evaluated in vitro by chick embryo chorioallantoic membrane assay, wound healing assay and tube formation assay. Corneal barrier and blood-retina barrier were constructed in vitro to investigate the penetration ability of Tat PTD-Endostatin-RGD. Western blot was used to detect the integrin αvβ3 expression level in rat retina microvascular endothelial cells which was stimulated by S-nitroso-N-acetylpenicillamine. The binding affinity of Tat PTD-Endostatin-RGD to integrin αvβ3 was investigated by evaluating the penetration ability on blood-retina barriers treated with S-nitroso-N-acetylpenicillamine. The pharmacodynamics and efficacy analysis were further carried out in the oxygen-induced retinopathy model in vivo. In addition, the pharmacokinetic profile via eye drops was studied on a C57BL/6 mice model. Result Tat PTD-Endostatin-RGD showed high anti-angiogenesis activity and high ability to penetrate these two barriers in vitro. The Western blot results indicated S-nitroso-N-acetylpenicillamine upregulated the expression level of integrin αvβ3 in a dose-dependent manner. Tat PTD-Endostatin-RGD showed a high affinity to rat retina microvascular endothelial cells treated with S-nitroso-N-acetylpenicillamine. The results showed that Tat PTD-Endostatin-RGD could inhibit abnormal angiogenesis in retina via eye drops. Conclusion Tat PTD-Endostatin-RGD showed high penetration ability through ocular barriers, bound specifically to integrin αvβ3 and effectively inhibited the abnormal angiogenesis. General significance Tat PTD-Endostatin-RGD represents a potent novel drug applied via eye drops for fundus oculi neovascularization diseases.

Original languageEnglish (US)
Pages (from-to)2137-2147
Number of pages11
JournalBiochimica et Biophysica Acta - General Subjects
Volume1860
Issue number10
DOIs
StatePublished - Oct 1 2016
Externally publishedYes

Fingerprint

Angiogenesis Inhibitors
Ophthalmic Solutions
Retina
S-Nitroso-N-Acetylpenicillamine
Integrins
Proteins
Assays
Endothelial cells
Rats
Blood
Endothelial Cells
Fundus Oculi
Western Blotting
Pharmacodynamics
Retinal Neovascularization
Chorioallantoic Membrane
Intravitreal Injections
Pharmacokinetics
Tat PTD-endostatin
Diabetic Retinopathy

Keywords

  • Blood-retina barrier
  • Corneal barriers
  • Neovascularization
  • Oxygen-induced retinopathy

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Tat PTD-Endostatin-RGD : A novel protein with anti-angiogenesis effect in retina via eye drops. / Li, Yan; Li, Lian; Li, Zhiwei; Sheng, Juzheng; Zhang, Xinke; Feng, Danyang; Zhang, Xu; Yin, Fengxin; Wang, Aijun; Wang, Fengshan.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1860, No. 10, 01.10.2016, p. 2137-2147.

Research output: Contribution to journalArticle

Li, Yan ; Li, Lian ; Li, Zhiwei ; Sheng, Juzheng ; Zhang, Xinke ; Feng, Danyang ; Zhang, Xu ; Yin, Fengxin ; Wang, Aijun ; Wang, Fengshan. / Tat PTD-Endostatin-RGD : A novel protein with anti-angiogenesis effect in retina via eye drops. In: Biochimica et Biophysica Acta - General Subjects. 2016 ; Vol. 1860, No. 10. pp. 2137-2147.
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title = "Tat PTD-Endostatin-RGD: A novel protein with anti-angiogenesis effect in retina via eye drops",
abstract = "Background Diabetic retinopathy is a leading cause of blindness. The objective was to design a novel fusion protein, Tat PTD-Endostatin-RGD, to treat retinal neovascularization via eye drops instead of traditional intravitreal injection trepapeutical methods. Method The anti-angiogenesis ability was evaluated in vitro by chick embryo chorioallantoic membrane assay, wound healing assay and tube formation assay. Corneal barrier and blood-retina barrier were constructed in vitro to investigate the penetration ability of Tat PTD-Endostatin-RGD. Western blot was used to detect the integrin αvβ3 expression level in rat retina microvascular endothelial cells which was stimulated by S-nitroso-N-acetylpenicillamine. The binding affinity of Tat PTD-Endostatin-RGD to integrin αvβ3 was investigated by evaluating the penetration ability on blood-retina barriers treated with S-nitroso-N-acetylpenicillamine. The pharmacodynamics and efficacy analysis were further carried out in the oxygen-induced retinopathy model in vivo. In addition, the pharmacokinetic profile via eye drops was studied on a C57BL/6 mice model. Result Tat PTD-Endostatin-RGD showed high anti-angiogenesis activity and high ability to penetrate these two barriers in vitro. The Western blot results indicated S-nitroso-N-acetylpenicillamine upregulated the expression level of integrin αvβ3 in a dose-dependent manner. Tat PTD-Endostatin-RGD showed a high affinity to rat retina microvascular endothelial cells treated with S-nitroso-N-acetylpenicillamine. The results showed that Tat PTD-Endostatin-RGD could inhibit abnormal angiogenesis in retina via eye drops. Conclusion Tat PTD-Endostatin-RGD showed high penetration ability through ocular barriers, bound specifically to integrin αvβ3 and effectively inhibited the abnormal angiogenesis. General significance Tat PTD-Endostatin-RGD represents a potent novel drug applied via eye drops for fundus oculi neovascularization diseases.",
keywords = "Blood-retina barrier, Corneal barriers, Neovascularization, Oxygen-induced retinopathy",
author = "Yan Li and Lian Li and Zhiwei Li and Juzheng Sheng and Xinke Zhang and Danyang Feng and Xu Zhang and Fengxin Yin and Aijun Wang and Fengshan Wang",
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T2 - A novel protein with anti-angiogenesis effect in retina via eye drops

AU - Li, Yan

AU - Li, Lian

AU - Li, Zhiwei

AU - Sheng, Juzheng

AU - Zhang, Xinke

AU - Feng, Danyang

AU - Zhang, Xu

AU - Yin, Fengxin

AU - Wang, Aijun

AU - Wang, Fengshan

PY - 2016/10/1

Y1 - 2016/10/1

N2 - Background Diabetic retinopathy is a leading cause of blindness. The objective was to design a novel fusion protein, Tat PTD-Endostatin-RGD, to treat retinal neovascularization via eye drops instead of traditional intravitreal injection trepapeutical methods. Method The anti-angiogenesis ability was evaluated in vitro by chick embryo chorioallantoic membrane assay, wound healing assay and tube formation assay. Corneal barrier and blood-retina barrier were constructed in vitro to investigate the penetration ability of Tat PTD-Endostatin-RGD. Western blot was used to detect the integrin αvβ3 expression level in rat retina microvascular endothelial cells which was stimulated by S-nitroso-N-acetylpenicillamine. The binding affinity of Tat PTD-Endostatin-RGD to integrin αvβ3 was investigated by evaluating the penetration ability on blood-retina barriers treated with S-nitroso-N-acetylpenicillamine. The pharmacodynamics and efficacy analysis were further carried out in the oxygen-induced retinopathy model in vivo. In addition, the pharmacokinetic profile via eye drops was studied on a C57BL/6 mice model. Result Tat PTD-Endostatin-RGD showed high anti-angiogenesis activity and high ability to penetrate these two barriers in vitro. The Western blot results indicated S-nitroso-N-acetylpenicillamine upregulated the expression level of integrin αvβ3 in a dose-dependent manner. Tat PTD-Endostatin-RGD showed a high affinity to rat retina microvascular endothelial cells treated with S-nitroso-N-acetylpenicillamine. The results showed that Tat PTD-Endostatin-RGD could inhibit abnormal angiogenesis in retina via eye drops. Conclusion Tat PTD-Endostatin-RGD showed high penetration ability through ocular barriers, bound specifically to integrin αvβ3 and effectively inhibited the abnormal angiogenesis. General significance Tat PTD-Endostatin-RGD represents a potent novel drug applied via eye drops for fundus oculi neovascularization diseases.

AB - Background Diabetic retinopathy is a leading cause of blindness. The objective was to design a novel fusion protein, Tat PTD-Endostatin-RGD, to treat retinal neovascularization via eye drops instead of traditional intravitreal injection trepapeutical methods. Method The anti-angiogenesis ability was evaluated in vitro by chick embryo chorioallantoic membrane assay, wound healing assay and tube formation assay. Corneal barrier and blood-retina barrier were constructed in vitro to investigate the penetration ability of Tat PTD-Endostatin-RGD. Western blot was used to detect the integrin αvβ3 expression level in rat retina microvascular endothelial cells which was stimulated by S-nitroso-N-acetylpenicillamine. The binding affinity of Tat PTD-Endostatin-RGD to integrin αvβ3 was investigated by evaluating the penetration ability on blood-retina barriers treated with S-nitroso-N-acetylpenicillamine. The pharmacodynamics and efficacy analysis were further carried out in the oxygen-induced retinopathy model in vivo. In addition, the pharmacokinetic profile via eye drops was studied on a C57BL/6 mice model. Result Tat PTD-Endostatin-RGD showed high anti-angiogenesis activity and high ability to penetrate these two barriers in vitro. The Western blot results indicated S-nitroso-N-acetylpenicillamine upregulated the expression level of integrin αvβ3 in a dose-dependent manner. Tat PTD-Endostatin-RGD showed a high affinity to rat retina microvascular endothelial cells treated with S-nitroso-N-acetylpenicillamine. The results showed that Tat PTD-Endostatin-RGD could inhibit abnormal angiogenesis in retina via eye drops. Conclusion Tat PTD-Endostatin-RGD showed high penetration ability through ocular barriers, bound specifically to integrin αvβ3 and effectively inhibited the abnormal angiogenesis. General significance Tat PTD-Endostatin-RGD represents a potent novel drug applied via eye drops for fundus oculi neovascularization diseases.

KW - Blood-retina barrier

KW - Corneal barriers

KW - Neovascularization

KW - Oxygen-induced retinopathy

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