School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.
Proteomics Clin Appl. 2008 May;2(5):762-75. doi: 10.1002/prca.200780094.
It is estimated that 37 million people worldwide suffer from blindness and 124 million people have impaired vision. While the relatively recently developed therapies, antivascular endothelial growth factor inhibitors for the treatment of age-related macular degeneration, and prostaglandin analogues for the treatment of glaucoma are beneficial for some patients, there are many individuals with sight-threatening diseases for whom no effective pharmacological therapy is available. For many of these diseases, the molecular mechanisms remain to be comprehensively elucidated, thus precluding the design of successful therapies against specific pathological targets. The current review summarises recent attempts to elucidate molecular mechanisms of ocular diseases, including diabetic retinal disease, age-related macular degeneration and inherited blindness using proteomic methodologies. A novel hypothesis can be generated from global protein expression analysis of disease tissue, which can then be addressed with cellular and in vivo functional studies. For example, the identification of extracellular carbonic anhydrase from the vitreous of diabetic retinopathy patients using MS based proteomics led to the elucidation of a new pathway involved in intraretinal edema, which could be inhibited by a number of agents targeting different proteins in this pathway in relevant animal models. The potential of protein biomarkers for diagnosis and the identification of novel disease mechanisms are also discussed.
据估计，全球有 3700 万人失明，1.24 亿人视力受损。虽然最近开发的一些疗法，如血管内皮生长因子抑制剂治疗年龄相关性黄斑变性，和前列腺素类似物治疗青光眼，对一些患者有益，但仍有许多患有威胁视力疾病的患者，目前尚无有效的药物治疗方法。对于这些疾病中的许多疾病，其分子机制仍有待全面阐明，从而无法针对特定的病理靶标设计成功的治疗方法。本综述总结了最近使用蛋白质组学方法阐明眼部疾病（包括糖尿病视网膜病变、年龄相关性黄斑变性和遗传性失明）分子机制的尝试。可以从疾病组织的全局蛋白质表达分析中生成新的假说，然后用细胞和体内功能研究来解决。例如，通过基于 MS 的蛋白质组学从糖尿病视网膜病变患者的玻璃体中鉴定出细胞外碳酸酐酶，从而阐明了一个新的参与视网膜内水肿的途径，该途径可被相关动物模型中靶向该途径中不同蛋白质的多种药物抑制。还讨论了蛋白质生物标志物在诊断和鉴定新疾病机制方面的潜力。
