Central serous chorioretinopathy mouse model

Nm3342小鼠可能是研究浆液性脱离和CSR的第一个临床合适的动物模型。我们研究的一个早期目标是确定突变和野生型小鼠之间的RPE和脉络膜是否存在基因差异，这种差异可能会扰乱调节并允许液体泄漏。在这些突变体中，脉络膜或RPE细胞可能出现异常，封闭细胞外间隙的紧密连接可能受到影响，也可能出现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的异常，或者异常是否只有在视网膜脱离后才会出现。孔源性脱离(液体流经视网膜上的孔洞或破裂)在视网膜中造成许多快速的细胞变化。严重的脱离是否会导致类似的变化尚不清楚。目前在人类CSR患者中的观察表明，光感受器层发生了退行性变化，但其性质尚不清楚。我们将确定是否在小鼠中发生光感受器退化和细胞死亡，以及是否存在神经元或神经胶质重塑，这可能预测人类CSR患者视觉缺陷的机制。孔源性脱离后，许多免疫反应基因上调，小胶质细胞激活。我们将确定在nm3342小鼠脱离后是否会出现类似的反应。因此，微阵列分析比较突变和野生型小鼠视网膜在分离发生前后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剥离的基因表达进行比较也是重要的。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，并有助于指导nm3342的细胞特性。我们将进行试点研究，以确定之前测试的小分子是否能解决nm3342小鼠的脱离，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，这是理解人类CSR的重要第一步。

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.