Human Corneal Model for Ocular Irritation Assay

用于眼刺激测定的人类角膜模型

• 批准号: 7538039
• 负责人: Yulia Kaluzhny
• 金额: $ 23.33万
• 依托单位: MATTEK CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7538039
• 关键词: Address; Adherent Culture; Amendment; Animal Testing; Animal Testing Alternatives; Animal Welfare; Animals; Area; Biological Assay; Cell Separation; Cells; Chemical Exposure; Chemicals; Clinical; Condition; Cornea; Corneal Endothelium; Corneal Injury; Cosmetics; Data; Depth; Dermal; Development; Epithelial; Epithelial Cells; European; Evaluation; Exposure to; Eye; Eye Injuries; Generations; Goals; Human; In Vitro; Industry; Injury; Irritants; Laws; Methods; Modeling; Oryctolagus cuniculus; Pathology; Pharmacologic Substance; Phase; Physiology; Property; Protocols documentation; Public Health; Range; Recovery; Reliance; Reproducibility; Research; Safety; Sales; Scientist; Testing; Thick; Time; Tissue Model; Tissues; Variant; Wound Healing; base; corneal epithelium; experience; improved; in vitro Assay; in vivo Model; irritation; member; monolayer; research study; response; surfactant; tool

DESCRIPTION (provided by applicant): Replacement of the Draize rabbit eye test for ocular irritancy testing remains an elusive goal. Although monolayer cultures and stratified corneal epithelial tissues have been developed and are useful as initial screens for ocular irritancy, they are not capable of completely modeling the interaction of exogenous chemical with human corneal tissue. For instance, protocols developed with current tissue models correctly identify a high percentage of ocular irritants (~ 95%) but misclassify a large percentage of non-irritants as irritants (~33%). Also, these models are not capable of modeling extent of injury and time to recovery following chemical insult. Thus, animal or human clinical tests are still needed to gain a compete picture of the effects of chemical exposure to the eye. The current application will develop a corneal full thickness (CFT) tissue model compromised of endothelial, stromal, and epithelial components. The CFT tissue will contain human cells and develop tissue barrier properties that are comparable to native corneal tissue. Because of its improved barrier, the CFT will avoid the misclassification of non-irritants. In addition, the CFT tissue will be useful in determining the extent of injury and time to recovery following noxious chemical exposure. Due to these enhanced capabilities, the CFT will provide toxicologists and scientists with a tool that will dramatically decrease, if not eliminate entirely, the need for animal testing to determine ocular irritancy. PUBLIC HEALTH RELEVANCE: Safety assessment of all new chemicals and products requires evaluation of potential ocular irritancy in case of intentional or unintentional exposure to the eye. Current animal-based test methods are sup-optimal because of animal welfare concerns and in vitro methods lack the complexity required to completely model in vivo responses. We will develop a corneal full thickness tissue and in vitro test methods that will dramatically reduce or eliminate the need to use animals to assess ocular irritancy of chemicals and products.

描述（由申请人提供）：取代用于眼刺激性测试的 Draize 兔眼测试仍然是一个难以实现的目标。尽管单层培养物和分层角膜上皮组织已被开发出来并且可用作眼部刺激性的初始筛选，但它们不能完全模拟外源化学物质与人角膜组织的相互作用。例如，使用当前组织模型开发的方案正确识别了高比例的眼部刺激物（约 95%），但将大部分非刺激物错误分类为刺激物（约 33%）。此外，这些模型无法模拟化学损伤后的损伤程度和恢复时间。因此，仍然需要动物或人体临床测试来全面了解化学品接触对眼睛的影响。目前的申请将开发一种由内皮、基质和上皮成分组成的角膜全层（CFT）组织模型。 CFT 组织将含有人类细胞，并具有与天然角膜组织相当的组织屏障特性。由于其屏障功能得到改善，CFT 将避免对非刺激物的错误分类。此外，CFT 组织将有助于确定有毒化学物质暴露后的损伤程度和恢复时间。由于这些增强的功能，CFT 将为毒理学家和科学家提供一种工具，即使不能完全消除，也将大大减少通过动物测试来确定眼部刺激性的需要。公共健康相关性：对所有新化学品和产品的安全评估需要评估有意或无意接触眼睛时潜在的眼部刺激性。由于动物福利问题，当前基于动物的测试方法不是最佳的，并且体外方法缺乏完全模拟体内反应所需的复杂性。我们将开发角膜全层组织和体外测试方法，这将大大减少或消除使用动物来评估化学品和产品对眼部刺激性的需要。