a Department of Ophthalmology , Duke University School of Medicine , Durham , NC , USA.
b Department of Pathology , Duke University School of Medicine , Durham , NC , USA.
Expert Opin Drug Discov. 2018 Apr;13(4):359-377. doi: 10.1080/17460441.2018.1430136. Epub 2018 Jan 30.
The impact of vision debilitating diseases is a global public health concern, which will continue until effective preventative and management protocols are developed. Two retinal diseases responsible for the majority of vision loss in the working age adults and elderly populations are diabetic retinopathy (DR) and age-related macular degeneration (AMD), respectively. Model systems, which recapitulate aspects of human pathology, are valid experimental modalities that have contributed to the identification of signaling pathways involved in disease development and consequently potential therapies. Areas covered: The pathology of DR and AMD, which serve as the basis for designing appropriate models of disease, is discussed. The authors also review in vitro and in vivo models of DR and AMD and evaluate the utility of these models in exploratory and pre-clinical studies. Expert opinion: The complex nature of non-Mendelian diseases such as DR and AMD has made identification of effective therapeutic treatments challenging. However, the authors believe that while in vivo models are often criticized for not being a 'perfect' recapitulation of disease, they have been valuable experimentally when used with consideration of the strengths and limitations of the experimental model selected and have a place in the drug discovery process.
致盲性疾病的影响是一个全球性的公共卫生关注点，这种影响将持续存在，直到开发出有效的预防和管理方案。两种视网膜疾病分别是糖尿病性视网膜病变（DR）和年龄相关性黄斑变性（AMD），导致了工作年龄段成年人和老年人群体视力丧失的大部分原因。重现人类病理学某些方面的模型系统是有效的实验方式，有助于确定与疾病发展相关的信号通路，进而发现潜在的治疗方法。涵盖领域：本文讨论了 DR 和 AMD 的病理学，这是设计适当疾病模型的基础。作者还回顾了 DR 和 AMD 的体外和体内模型，并评估了这些模型在探索性和临床前研究中的应用。专家意见：DR 和 AMD 等非孟德尔疾病的复杂性使得确定有效的治疗方法具有挑战性。然而，作者认为，尽管体内模型常常因其不能“完美”再现疾病而受到批评，但当考虑到所选实验模型的优势和局限性并将其应用于实验时，它们在实验中具有价值，并在药物发现过程中占有一席之地。
