年龄相关性黄斑变性（AMD）是50岁以上人群失明的首要原因，日益增多的证据表明β淀粉样蛋白（Aβ）与玻璃膜疣的形成及早期AMD病变密切相关。已报道针对Aβ的被动免疫治疗在AMD小鼠模型（APOE4-HFC）上取得良好效果，而主动免疫更适合于AMD这类慢性疾病，因此我们推测针对Aβ的主动免疫治疗可更好的干预早期AMD。本课题拟采用前期构建的病理特征更为典型的早期AMD小鼠模型（ELOVL4转基因小鼠）进一步证实Aβ与早期AMD病变的相关性，并采用对具有相似病理特征的阿尔茨海默病小鼠模型治疗效果突出的新型Aβ多肽疫苗（Aβ-HSP60），对ELOVL4转基因小鼠进行主动免疫治疗，通过观测眼部相关指标的变化来观察其对早期AMD的疗效，从而验证我们的假说，为进一步阐明Aβ可作为早期AMD免疫治疗的新靶标奠定基础，同时建立以Aβ为靶标的早期AMD免疫治疗研究模型，对探索早期AMD的治疗具有重要意义。

Age-related Macular Degeneration (AMD) is the primary cause of blindness in senior people over 50yrs. A number of previous findings indicated that the deposit of Beta-Amyloid (Aβ) in drusen plays an important role in the pathogenesis of early-stage AMD. Previous report showed that the passive immune therapy targeting at Aβ had promising effects in the mouse model of AMD (APOE4-HFC). Due to the fact that the active immune therapy is usually more efficient in treating chronic diseases, we propose that the active immune therapy targeting at Aβ could become a more promising therapeutic approach in delaying the progress of early-stage AMD. The current proposal will: 1) explore the relationship of Aβ and the early-stage AMD in the ELOVL4 transgenic mouse, which model is the protypical pathological model of early-stage AMD; 2) further evaluate the clinical application of the Aβ-HSP60 peptide vaccine in the transgenic mouse mentioned above. The active immune therapy of Aβ-HSP60 peptide vaccine was known to have pronounced effect in the treatment of Alzheimer's disease, which disease has the similar pathogenesis as AMD. The therapeutic evaluation of the Aβ-HSP60 peptide vaccine will rely on the assessment of various characteristics of retina. The current proposal is significant in exploring the critical role of Aβ in the pathogenesis of early-stage AMD as well as evaluating the active immune therapy targeting at Aβ in the specific transgenic mouse model of AMD, which will lead to a novel therapeutic regimen of early-stage AMD in the future.