背景:视网膜色素上皮(RPE),位于神经感觉视网膜和下面的脉络膜之间的一层色素细胞,在维持感光细胞的功能完整性以及介导神经感觉视网膜和脉络膜之间的通讯中起着至关重要的作用。先前的研究已经证明了通过一系列不同的作用机制来减轻视网膜变性疾病的发展和进展的选择类固醇的神经营养作用。
方法:这里,我们确定了主要的类固醇激素信号通路及其控制类固醇激素信号通路的关键功能蛋白成分,可能参与视网膜变性过程的缓解或传播,来自人类蛋白质组数据集的视网膜周边相对丰度,黄斑,和中央凹。
结果:雄激素,糖皮质激素,在脉络膜-视网膜色素上皮复合物的这三个解剖学上不同的区域内,鉴定和孕酮信号网络并显示出不同的分布模式。经典和非经典雌激素和盐皮质激素受体未被鉴定。
结论:确定的差异分布模式表明两种对慢性神经退行性疾病过程的选择性易感性,以及药物靶标发现和新药开发的潜在底物集中在脉络膜RPE中的类固醇信号通路。
BACKGROUND: The retinal pigment epithelium (RPE), a layer of pigmented cells that lies between the neurosensory retina and the underlying choroid, plays a critical role in maintaining the functional integrity of photoreceptor cells and in mediating communication between the neurosensory retina and choroid. Prior studies have demonstrated neurotrophic effects of select steroids that mitigate the development and progression of retinal degenerative diseases via an array of distinct mechanisms of action.
METHODS: Here, we identified major steroid hormone signaling pathways and their key functional protein constituents controlling steroid hormone signaling, which are potentially involved in the mitigation or propagation of retinal degenerative processes, from human proteome datasets with respect to their relative abundances in the retinal periphery, macula, and fovea.
RESULTS: Androgen, glucocorticoid, and progesterone signaling networks were identified and displayed differential distribution patterns within these three anatomically distinct regions of the choroid-retinal pigment epithelial complex. Classical and non-classical estrogen and mineralocorticoid receptors were not identified.
CONCLUSIONS: Identified differential distribution patterns suggest both selective susceptibility to chronic neurodegenerative disease processes, as well as potential substrates for drug target discovery and novel drug development focused on steroid signaling pathways in the choroid-RPE.