A bovine eye model for steroid-induced glaucoma

类固醇诱发青光眼的牛眼模型

• 批准号: 7266926
• 负责人: Oscar A Candia
• 金额: $ 16.46万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7266926
• 关键词: Adrenal Cortex Hormones; Animal Model; Bos taurus; Cattle; Data; Development; Elevation; Event; Eye; Future; Gene Expression; Genes; Genetic; Glaucoma; Human; Individual; Investigation; Lead; Libraries; Modeling; Molecular; Open-Angle Glaucoma; Optic Disk; Optic Nerve; Organ Culture Techniques; Pathology; Physiologic Intraocular Pressure; Pilot Projects; Primary Open Angle Glaucoma; Resources; Retina; Steroids; Structure; System; Testing; Time; Tissue-Specific Gene Expression; Tissues; Trabecular meshwork structure; Week; cDNA Library; high intraocular pressure; in vivo; myocilin; novel; optic nerve disorder; response; size

DESCRIPTION (provided by applicant): Glucocorticosteroids are known to cause intraocular pressure (IOP) elevation in susceptible individuals that can lead to glaucomatous optic neuropathy. Steroid-induced glaucoma resembles primary open angle glaucoma in the mechanism of IOP elevation and in the optic neuropathy. Some of the cellular & molecular mechanisms leading to IOP elevation have been studied in tissue and/or organ culture but not in vivo. Thus a reliable animal model of steroid-induced glaucoma would be extremely valuable as an in vivo system for testing specific hypotheses about these mechanisms. We have found that IOP significantly increases in bovine eyes treated topically with corticosteroids for more than 4 weeks. The consistency of the steroid response in this species, together with the size of the bovine eye and its similarities to the human eye make it an ideal animal model for steroid-induced glaucoma. As the first steps towards establishing the suitability of this model for future studies, we propose an investigation to achieve the following three specific aims: 1. To determine the histopathological changes that occur in major structures associated with glaucoma (TM, retina and optic nerve head (ONH)) during the course of steroid-induced IOP elevation in the bovine eye and to determine the correlation of each change with the level and duration of IOP elevation. 2. To generate cDNA libraries of differentially expressed genes in the TM, retina and ONH at various time points during the steroid-induced IOP elevation. Such libraries will be screened in the future for novel genes that are involved in steroid-induced IOP elevation as well as genes that may be involved in the response of the retina and ONH when IOP is elevated by corticosteroids. 3. To determine differentially expressed genes in the TM, retina and ONH at specific time points during the steroid-induced IOP elevation using microarrays. Determination of these changes will allow us to potentially determine the sequence of molecular events responsible for the development of glaucomatous pathology.

描述（由申请方提供）：已知糖皮质激素可导致易感个体的眼内压（IOP）升高，进而导致青光眼性视神经病变。类固醇诱发的青光眼在眼压升高机制和视神经病变方面与原发性开角型青光眼相似。一些导致IOP升高的细胞和分子机制已在组织和/或器官培养中进行了研究，但尚未在体内进行研究。因此，一个可靠的类固醇诱导的青光眼动物模型将是非常有价值的，作为一个在体内系统，用于测试这些机制的具体假设。我们发现，用皮质类固醇局部治疗超过4周的牛眼的IOP显著增加。该物种中类固醇反应的一致性，以及牛眼的大小及其与人眼的相似性，使其成为类固醇诱导的青光眼的理想动物模型。作为建立该模型适用于未来研究的第一步，我们提出了一项调查，以实现以下三个具体目标： 1.确定青光眼相关主要结构的组织病理学变化 (TM视网膜和视神经乳头（ONH））的变化，并确定每种变化与IOP升高的水平和持续时间的相关性。 2.建立激素诱导的眼压升高过程中不同时间点TM、视网膜和ONH中差异表达基因的cDNA文库。将来将对这些文库进行筛选，以寻找参与类固醇诱导的IOP升高的新基因以及可能参与皮质类固醇升高IOP时视网膜和ONH反应的基因。 3.应用基因芯片检测激素诱导的眼压升高过程中特定时间点TM、视网膜和ONH中差异表达的基因。这些变化的测定将使我们能够潜在地确定负责脑胶质瘤病理学发展的分子事件的顺序。

项目成果

Morphologic changes in the outflow pathways of bovine eyes treated with corticosteroids.

用皮质类固醇治疗的牛眼流出途径的形态变化。

• DOI: 10.1167/iovs.09-4742
• 发表时间: 2010
• 期刊: Investigative ophthalmology & visual science
• 影响因子: 4.4
• 作者: Tektas,Ozan-Yüksel;Hammer,ChristianManfred;Danias,John;Candia,Oscar;Gerometta,Rosana;Podos,StevenM;Lütjen-Drecoll,Elke
• 通讯作者: Lütjen-Drecoll,Elke