视网膜变性疾病是一类严重危害人类视功能的难治性致盲眼病，新兴的基因治疗目前效果不佳。视网膜神经变性多伴严重的血管变性退化，血供缺乏将进一步加重神经细胞变性损伤，因此血管保护和重建是视网膜变性疾病综合治疗的关键环节。我们既往研究发现血小板源性生长因子(PDGF-C)可促进视网膜血管的存活和再生(PNAS,2014)，并发现A1AT可调控小胶质细胞极化改变炎症微环境，影响血管生长因子的功能效应。由此，我们创新性提出PDGF-C促进血管再生联合A1AT调控小胶质细胞极化可能是有效重建血管，治疗视网膜变性疾病的新策略。本项目应用多种视网膜变性疾病动物模型探索该治疗策略的有效性和安全性及其促基因修复治疗的作用，研究PDGF-C联合A1AT促血管细胞协同作用重建血管功能的分子机制。研究结果将揭示血管重建在视网膜变性疾病治疗中的重要性，为其临床应用奠定基础，开拓视网膜变性疾病治疗的新策略。

Retinal degenerative diseases are one of the leading causes of blindness. Gene therapy has attracted fervent interest as a potential new treatment. However, its effectiveness is disappointing in both animal models and clinical trials. It has long been neglected that retinal degenerative diseases are often accompanied by serious vascular degeneration and regression, which promote the damage of the photoreceptors and retinal pigment epithelium and inhibit their recovery. Therefore, vascular protection and revascularization have the potential to promote neural survival and might be crucial for the treatment. Our previous study showed that platelet derived growth factor (PDGF-C) plays a pivotal role in maintaining the survival and growth of blood vessel. We also found that A1AT, a novel immunomodulation agent, is able to regulate microglia polarization, leading to reduced inflammation in the microenvironment, which may benefit the vascular growth factors to exert their biological functions. Based on our previous work, we hypothesize that “Combined therapy of PDGF-C and A1AT may be a novel strategy for the treatment of retinal degenerative diseases”. In this study, we plan to use different retinal degenerative disease models to investigate the possibility and efficacy of combining PDGF-C and A1AT to treat such diseases, and explore the molecular mechanisms involved. The outcome of this study will not only provide new insights into the revascularization in treating retinal neurodegenerative diseases, but may also contribute to the development of new therapeutic strategy for retinal degenerative diseases.