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眼科药物开发的转化临床前药理疾病模型。

Translational Preclinical Pharmacologic Disease Models for Ophthalmic Drug Development.

机构信息

Biological Research, Allergan plc, 2525 Dupont Drive, Irvine, California, 92612, USA.

出版信息

Pharm Res. 2019 Feb 25;36(4):58. doi: 10.1007/s11095-019-2588-5.

Abstract

Preclinical models of human diseases are critical to our understanding of disease etiology, pathology, and progression and enable the development of effective treatments. An ideal model of human disease should capture anatomical features and pathophysiological mechanisms, mimic the progression pattern, and should be amenable to evaluating translational endpoints and treatment approaches. Preclinical animal models have been developed for a variety of human ophthalmological diseases to mirror disease mechanisms, location of the affected region in the eye and severity. These models offer clues to aid in our fundamental understanding of disease pathogenesis and enable progression of new therapies to clinical development by providing an opportunity to gain proof of concept (POC). Here, we review preclinical animal models associated with development of new therapies for diseases of the ocular surface, glaucoma, presbyopia, and retinal diseases, including diabetic retinopathy and age-related macular degeneration (AMD). We have focused on summarizing the models critical to new drug development and described the translational features of the models that contributed to our understanding of disease pathogenesis and establishment of preclinical POC.

摘要

人类疾病的临床前模型对于我们理解疾病的病因、病理学和进展至关重要,并且能够开发出有效的治疗方法。一个理想的人类疾病模型应该能够捕捉到解剖学特征和生理学机制,模拟疾病的进展模式,并且能够评估转化终点和治疗方法。已经为各种人类眼科疾病开发了临床前动物模型,以反映疾病机制、受影响区域在眼睛中的位置和严重程度。这些模型提供了线索,有助于我们深入了解疾病的发病机制,并通过提供获得概念验证 (POC) 的机会,使新疗法的进展能够进入临床开发。在这里,我们回顾了与眼部表面疾病、青光眼、老花眼和视网膜疾病(包括糖尿病视网膜病变和年龄相关性黄斑变性 (AMD))的新疗法开发相关的临床前动物模型。我们重点总结了对新药开发至关重要的模型,并描述了有助于我们了解疾病发病机制和建立临床前 POC 的模型的转化特征。

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