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In vitro reconstructed 3D corneal tissue models for ocular toxicology and ophthalmic drug development
In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2021-02-05 , DOI: 10.1007/s11626-020-00533-7
Yulia Kaluzhny 1 , Mitchell Klausner 1
Affiliation  

Testing of all manufactured products and their ingredients for eye irritation is a regulatory requirement. In the last two decades, the development of alternatives to the in vivo Draize eye irritation test method has substantially advanced due to the improvements in primary cell isolation, cell culture techniques, and media, which have led to improved in vitro corneal tissue models and test methods. Most in vitro models for ocular toxicology attempt to reproduce the corneal epithelial tissue which consists of 4–5 layers of non-keratinized corneal epithelial cells that form tight junctions, thereby limiting the penetration of chemicals, xenobiotics, and pharmaceuticals. Also, significant efforts have been directed toward the development of more complex three-dimensional (3D) equivalents to study wound healing, drug permeation, and bioavailability. This review focuses on in vitro reconstructed 3D corneal tissue models and their utilization in ocular toxicology as well as their application to pharmacology and ophthalmic research. Current human 3D corneal epithelial cell culture models have replaced in vivo animal eye irritation tests for many applications, and substantial validation efforts are in progress to verify and approve alternative eye irritation tests for widespread use. The validation of drug absorption models and further development of models and test methods for many ophthalmic and ocular disease applications is required.



中文翻译:

用于眼毒理学和眼科药物开发的体外重建 3D 角膜组织模型

对所有制成品及其成分进行眼睛刺激性测试是一项监管要求。在过去的二十年中,由于原代细胞分离、细胞培养技术和培养基的改进,体内 Draize 眼刺激测试方法的替代方法的开发取得了实质性进展,这导致了体外角膜组织模型和测试的改进方法。大多数眼毒理学体外模型试图复制由 4-5 层非角化角膜上皮细胞组成的角膜上皮组织,这些细胞形成紧密的连接,从而限制了化学物质、异生物质和药物的渗透。此外,还致力于开发更复杂的三维 (3D) 等效物来研究伤口愈合、药物渗透和生物利用度。本综述侧重于体外重建的 3D 角膜组织模型及其在眼毒理学中的应用以及它们在药理学和眼科研究中的应用。当前的人类 3D 角膜上皮细胞培养模型已经在许多应用中取代了体内动物眼睛刺激测试,并且正在进行大量验证工作以验证和批准可广泛使用的替代眼睛刺激测试。需要对药物吸收模型进行验证,并进一步开发许多眼科和眼科疾病应用的模型和测试方法。当前的人类 3D 角膜上皮细胞培养模型已经在许多应用中取代了体内动物眼睛刺激测试,并且正在进行大量验证工作以验证和批准可广泛使用的替代眼睛刺激测试。需要对药物吸收模型进行验证,并进一步开发许多眼科和眼科疾病应用的模型和测试方法。当前的人类 3D 角膜上皮细胞培养模型已经在许多应用中取代了体内动物眼睛刺激测试,并且正在进行大量验证工作以验证和批准可广泛使用的替代眼睛刺激测试。需要对药物吸收模型进行验证,并进一步开发许多眼科和眼科疾病应用的模型和测试方法。

更新日期:2021-02-05
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