很多疾病（如糖尿病视网膜病变）引起眼部血管增生，使视功能受到严重损害，甚至失明。目前，该类疾病没有有效的治疗药物，其原因是由于眼球的屏障作用，局部用药药物不能到达眼底。本课题拟利用穿膜肽Tat PTD的穿膜作用和内皮抑素的抑制新生血管生成的作用，将二者通过基因工程的手段融合在一起，以期获得能够穿透眼球屏障的内皮抑素，达到通过简单的局部滴眼给药预防视网膜血管增生的目标。这一研究对探索大分子蛋白质眼部给药的新途径和视网膜病变的防治具有重要意义。.本项目的主要内容包括：①Tat PTD-内皮抑素的表达,复性分离纯化；②Tat PTD-内皮抑素融合蛋白的活性研究，包括对内皮细胞生长的抑制活性和抑制新生血管生成的活性；③Tat-PTD-内皮抑素融合蛋白穿透眼球屏障研究；④Tat PTD-内皮抑素融合蛋白抑制视网膜血管生成的作用研究。Tat-PTD-内皮抑素细胞水平穿透眼球屏障的机制研究。

Many diseases (such as diabetic retinopathy) can induce vascular proliferation of eyes which makes serious damage to visual fuction or even results in blindness. Due to the existence of ocular barriers, it is difficult for drugs to arrive at ocular fundus when admistrated via eye drops. Unitll now, there is no efficient drug to cure these ocular diseases. In this project, fusion protein, Tat protein transduction domain (Tat PTD)-endostatin, will be expressed in E.coli by biotechnology. The fusion protein is expected to cross ocular barriers via the help of Tat PTD and perform inhibiton effect of endostatin on vascular proliferation of retina. This project is of great significance for the prevention and treatment of retinopathy disease, and will provide a new way for the delivery of large protein drugs to ocular fundus. .The main research content of this project includes: ①Fusion expression, renaturation, purification of Tat PTD-endostatin; ②Investigation of inhibiton activity on cells and vascular proliferation of Tat PTD-endostatin; ③The ability to cross eye barriers of Tat PTD-endostatin; ④The pharmacodynamics of Tat PTD-endostatin on proliferative vascular retinopathy; ⑤The eye barrier penetrating mechanism of Tat PTD-endostain at cells level.