| First Author | Li Y | Year | 2016 |
| Journal | Biochim Biophys Acta | Volume | 1860 |
| Issue | 10 | Pages | 2137-47 |
| PubMed ID | 27233450 | Mgi Jnum | J:250804 |
| Mgi Id | MGI:6105258 | Doi | 10.1016/j.bbagen.2016.05.031 |
| Citation | Li Y, et al. (2016) Tat PTD-Endostatin-RGD: A novel protein with anti-angiogenesis effect in retina via eye drops. Biochim Biophys Acta 1860(10):2137-47 |
| abstractText | 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 alphavbeta3 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 alphavbeta3 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 alphavbeta3 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 alphavbeta3 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. |
