Tat PTD-Endostatin-RGD: A novel protein with anti-angiogenesis effect in retina via eye drops.
Biochim Biophys Acta
; 1860(10): 2137-47, 2016 10.
Article
en En
| MEDLINE
| ID: mdl-27233450
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 αvß3 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 αvß3 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 αvß3 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 αvß3 and effectively inhibited the abnormal angiogenesis. GENERALSIGNIFICANCE:
Tat PTD-Endostatin-RGD represents a potent novel drug applied via eye drops for fundus oculi neovascularization diseases.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oligopéptidos
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Proteínas Recombinantes de Fusión
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Neovascularización Retiniana
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Endostatinas
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Retinopatía Diabética
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Neovascularización Patológica
Límite:
Animals
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Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2016
Tipo del documento:
Article
País de afiliación:
China