Caveolae调控α1A-AR介导模拟失重大鼠眼脉络膜循环障碍的机制研究

航天飞行相关神经-眼综合征（SANS）作为制约人类长期太空生活工作的重要原因，主要表现为宇航员眼轴变短，脉络膜皱褶、视盘水肿等病理性改变。申请人课题组前期发现模拟失重8周后SD大鼠眼底脉络膜血流增多，其营养的外层视网膜出现明显退行性改变，视觉功能下降，但相关机制目前尚不清楚。脉络膜位于巩膜与视网膜之间，由小叶状血管丛和非血管平滑肌组成。Caveolae是介导模拟失重大鼠血管重塑的关键结构，α1A-AR是介导脉络膜收缩的重要受体，两者间可能存在相互作用。申请人认为模拟失重引起脉络膜Caveolae分布变化，进而调控α1A-AR受体内吞，引起脉络膜收缩异常，导致膜循环障碍，引起视网膜营养不良，出现退行性改变。为验证该假说，我们拟采用多种分子生物学方法阐明模拟失重大鼠脉络膜循环障碍致视网膜退行性改变的可能机制。该项目对于揭示SANS的发病机制及保障长期载人航天飞行具有重要的科学意义。

Spaceflight associated neuro-ocular syndrome (SANS) is an important factor that restricts long-time travel in space. The main manifestations of SANS are the shortened eye axis, the pathological changes such as choroidal folds and optic disc edema. Our previous research found that after 8 weeks, blood flow of choroid increased in SD rats of simulated weightlessness, and outer retina showed obvious degenerative changes and decreased visual function which nutrition is supplied by choroid. The underlying mechanism is still unclear. The choroid, located between the sclera and retina, is mainly composed of lobular vascular plexus and non-vascular smooth muscles. Caveolae is an important structure that regulates the vascular remodeling in simulated weightlessness. α1A-AR plays an important role in contraction of choroid. We believe that microgravity environment causes changes in number and distribution of Caveolae in choroid, regulating α1A-AR mediated contraction, resulting in choroidal circulation disorders. Then degenerative changes come into being in outer retina. In order to verify this hypothesis, we intend to use a variety of molecular biological methods to clarify the possible mechanism of simulated choroidal circulation disorders in mice retinal degenerative changes. This project is of great scientific significance for revealing the pathogenesis of SANS and ensuring long-term manned spaceflight.