眼部新生血管形成是许多致盲性眼病失明的主要原因。血管内皮生长因子(VEGF-A)是目前治疗该类疾病的靶基因，但其拮抗剂只对部分病人有效并易产生耐药性。因此揭示VEGF-A拮抗剂的抗药机理并筛选新的靶点成为目前本领域的热点。我们率先发现血小板源性生长因子PDGF-C/-D是除VEGF-A之外的强促血管生长因子，并在多个小鼠模型中得以验证。但是对于它们的作用机理及是否是导致VEGF-A拮抗剂抗性的原因则有待深入研究，而这些正是我们在研的国自然重点研究项目“PDGF-C和PDGF-D：眼新生血管性疾病防治的新靶点及其机制研究”的内容。瑞典林雪平大学的Lasse Jensen博士建立了斑马鱼研究低氧和炎症诱导的眼部新生血管形成的独特系统。我们将和Jensen博士合作，通过互访和人员培训，利用斑马鱼这一快速而相对简单的系统研究PDGF-C/D的机理以及和VEGF-A的关系，并将相关技术移植回国内，以加速加深现有国自然重点项目的研究。同时利用我们所长，帮助Jensen博士的团队提升小鼠模型方面的技术，达到互利双赢的目的，为将来的长期合作奠定基础。

Pathological angiogenesis is the primary cause of blindness and a common complication among ocular diseases. VEGF-A antagonists have been developed to treat these sickness in recent years. Despite relatively dramatic success compared to the past, many issues remain, among which are intrinsic and acquired drug resistance. Therefore, it is urgent to dissect the mechanisms causing the resistance and identify the novel targets to overcome it. .Previously we have found that PDGF-C/D are potent pro-angiogenic factors independent of VEGF-A in multiple mouse models. However, it is unclear how PDGF-C/D promote angiogenesis and if they are responsible for the drug resistance in the anti-VEGF-A therapies. We have proposed to investigate these issues in our ongoing NSFC project: “PDGF-C/D: the potential novel targets against ocular angiogenesis and their relevant mechanism”（81330021）..Dr. Lasse Jensen at Linköping University has developed a Zebrafish system focusing on pathological angiogenesis mediated by hypoxia and inflammation in adult retinae and choroids. .We propose to establish collaboration with Dr. Jensen’s group to take full advantage of the above Zebrafish system and our current mouse angiogenesis models to study the issues with regards to PDGF-C/D. By verifying the results from one system to another, we expect to intensify and accelerate the PDGF-C/D research. The major goal of this project is to benefit both sides with regard to technologies and scientific subjects through multiple mini-symposiums and young scientist training sessions held in both institutions. These initials will lead to a long-term collaboration in the future.

眼新生血管形成是许多难治性致盲性眼病失明的主要原因和共同病理过程。血管内皮生长因子（VEGF）是目前有效治疗眼新生血管性疾病的靶基因，但抗VEGF药物目前存在种种问题。本团队前期的研究发现血小板源性生长因子新成员PDGF-C和PDGF-D很可能是眼新生血管形成的新机制和防治眼新生血管性疾病的新靶点,并据此申请获得了国自然的重大项目的资助。本项中瑞合作交流项目依托于上述重大项目，希望通过和瑞典合作伙伴的交流从不同角度拓宽中瑞双方各自的研究思路，提升研究手段，培训各自研究团队年轻学者以及研究生，进而促进双方的科研产出，并为建立长期合作关系，将来共同申请更长期的国际合作基金奠定基础。在项目执行过程中，瑞典Lasse Jensen教授团队共访华两次，团队成员来华交流短期培训一次。我方对瑞典的访问由计划中的多次调整成实际执行中的一次, 团队成员参加了瑞典方面组织的欧盟夏季眼科技术培训班。由于项目资金到位较晚、互访审批程序过于冗长等问题，交流计划和内容做了相应的调整，最终达到了预期的目标。受益于与瑞典方的合作交流，我方团队的技术能力得到了进一步提升，多人熟练掌握了肿瘤模型的建立、炎症诱导角膜新生血管模型的建立及注意事项，并掌握了斑马鱼低氧诱导血管的相关技术，发表了与PDGF-C和PDGF-D相关的综述文章三篇，学术论文一篇，同时与瑞典方共同申请了2017 年的中瑞合作项目。综上所述，此次的中瑞项目合作达到了最初设定的目标。