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 journalArticlepeer-review

17 Scopus citations


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
Issue number10
StatePublished - Oct 1 2016
Externally publishedYes


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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology


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