Central serous chorioretinopathy mouse model

nm3342小鼠可能是临床第一个适合研究浆液性脱离和CSR的动物模型。我们研究的早期目标将是确定突变型和野生型小鼠之间的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泄漏。在这些突变体中，脉络膜细胞或RPE细胞可能异常，细胞间封闭细胞外空间的紧密连接可能受到影响，或者RPE细胞可能死亡。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（液体流经视网膜上的孔或裂口）在视网膜上造成许多快速的细胞变化。严重的分离是否会引起类似的变化尚不清楚。目前对人类CSR患者的观察表明，光感受器层发生退行性改变，但其性质尚不清楚。我们将确定小鼠是否发生光感受器变性和细胞死亡，以及是否存在神经元或胶质重塑，这可能预测人类CSR患者视觉缺陷的机制。孔源性脱离后，许多免疫应答基因上调，小胶质细胞活化。我们将确定nm3342小鼠脱离后是否会出现类似的反应。因此，微阵列分析来比较突变型和野生型小鼠视网膜分离前后的基因表达谱将是这个项目的关键组成部分。同样重要的是，比较相同持续时间的孔源性分离的基因表达。我们将通过高分辨率OCT获得nm3342小鼠眼部结构的时间线变化，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能解决nm3342小鼠的脱离问题，并开始探索nm3342 RPE细胞原代培养的方法。提出的实验应该有助于我们理解浆液性视网膜脱离的特殊特征，这是理解人类CSR的重要的第一步。

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.