Central serous chorioretinopathy mouse model

中心性浆液性脉络膜视网膜病变小鼠模型

• 批准号: 8149202
• 负责人: Sheldon Miller
• 金额: $ 3.12万
• 依托单位: NATIONAL EYE INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8149202
• 关键词: Serous; mouse model

The nm3342 mouse may be the first clinically appropriate animal model for studying serous detachment and CSR. An early goal of our study will be to determine if there are gene differences in the RPE and choroidal between mutant and wild type mice that may disrupt regulation and allow for fluid leakage. in In these mutants, the choroidal or RPE cells may be abnormal, tight junctions that seal the extracellular space between cells may be affected, or there may be RPE cell death . We will also determine if the mutation itself causes abnormalities in the neural retina or if abnormalities only arise after retinal detachment. Rhegmatogenous detachment (where fluid flows through a hole or break in the retina) creates many rapid cellular changes in the retina. Whether serous detachments cause similar changes is unknown. Current observations in human patients with CSR suggest degenerative changes in the photoreceptor layer, but their nature is unknown. We will determine if the photoreceptor degeneration and cell death occurs in the mice and if there is neuronal or glial remodeling that may predict mechanisms for visual imperfections in human CSR patients. An upregulation of many immune response genes and the activation of microglial cells occur after rhegmatogenous detachment. We will determine if similar responses occur after detachment in the nm3342 mice. Thus, microarray analysis to compare gene expression profiles in retinas of mutant and wild type mice before and after the detachments occur will be a critical component of this project. Comparisons to gene expression in rhegmatogenous detachments of the same duration will be important as well. We will obtain time-line ocular structural changes in nm3342 mice by high-resolution OCT, a powerful non-invasive technique that will provide additional structural data and help guide the cellular characterization of nm3342. We will do pilot studies to determine if previously tested small molecules resolve detachment in the nm3342 mice, and begin exploring methods for primary cultures of nm3342 RPE cells. The proposed experiments should help us understand the special characteristics of serous retinal detachments, an important first step to understanding CSR in humans.

nm3342小鼠可能是第一个临床上适用于研究浆液脱离和CSR的动物模型。我们研究的早期目标是确定突变型和野生型小鼠的 RPE 和脉络膜是否存在基因差异，这些差异可能会破坏调节并导致液体渗漏。在这些突变体中，脉络膜或RPE细胞可能出现异常，细胞间密封细胞外空间的紧密连接可能受到影响，或者可能出现RPE细胞死亡。我们还将确定突变本身是否会导致神经视网膜异常，或者异常是否仅在视网膜脱离后出现。孔源性脱离（液体流过视网膜上的孔或裂口）会在视网膜中造成许多快速的细胞变化。浆液性脱离是否会引起类似的变化尚不清楚。目前对患有 CSR 的人类患者的观察表明，感光层发生了退行性变化，但其性质尚不清楚。 我们将确定小鼠中是否发生光感受器变性和细胞死亡，以及是否存在可以预测人类 CSR 患者视觉缺陷机制的神经元或神经胶质重塑。孔源性脱离后会发生许多免疫反应基因的上调和小胶质细胞的激活。我们将确定 nm3342 小鼠脱离后是否会发生类似的反应。因此，通过微阵列分析来比较突变型和野生型小鼠在脱离发生前后视网膜中的基因表达谱将是该项目的关键组成部分。与相同持续时间的孔源性脱离中的基因表达进行比较也很重要。我们将通过高分辨率 OCT 获得 nm3342 小鼠的眼部结构变化的时间线，这是一种强大的非侵入性技术，将提供额外的结构数据并帮助指导 nm3342 的细胞表征。 我们将进行初步研究，以确定先前测试的小分子是否可以解决 nm3342 小鼠的脱离问题，并开始探索 nm3342 RPE 细胞的原代培养方法。拟议的实验应该有助于我们了解浆液性视网膜脱离的特殊特征，这是了解人类企业社会责任的重要第一步。