干眼症新机制：钙激活氯通道在结膜泪液分泌中的病理生理作用及其调控

The unbalance of homeostasis in tear secretion will bring out dry eye disease. There are more than 1 billion people suffering from dry eye at diferent degree. The incidecne of dry eye in population reaches 10 to 30 percents. The pathogenesis of dry eye is not fully elucidated until now, and there is lack of satisfactory treatments in clinics. In recent, conjunctival secretion was reported to be comprised of one fourth tear volumn. However, the associated mechanism and its role in dry eye was unclear. Our preliminary findings firstly showed that: 1. Physical tear secretion from conjunctiva is regulated by calcium-activated chloride channel (CaCC), and 2. The pathway of CaCC may be damaged in animal dry eyes. Based on these data, we proposed a possible new mechanism in dry eye: Tear secretion may take part in the the development and progess of dry eye through regulation of CaCC. In order to verify this hypothesis, several commonly used animal dry eye models which resemble clinical classification will be established and examined for investigating: 1. Is the damage of CaCC a common mechansim in all kinds of animal dry eyes? 2. And what is the key factor in the damage of CaCC pathway? 3. What’s the relationship between the CaCC damage and the reported inflammtory, hyperosmotic machanisms as well as secretion of accessory lacrimal gland in the pathogenesis of dry eye? 4. How to regulate the pathway of CaCC for creating new dry eye animal models or treating dry eye? The coming results of this project will answer the question whether CaCC can be a new target for intervening tear secretion. The completion of this project may reveal a new physical mechanism of tear seretion, and explore a brand new way in improving tear secretion for dry eyes in theory and practice.

泪液分泌稳态破坏会导致干眼症。全球有超十亿人口存在不同程度干眼症。目前其发病机制尚不完全清楚，临床也缺乏很好的治疗手段。最近研究发现结膜分泌占泪液总量的1/4左右，但相关机制及其在干眼症中的确切作用尚不清楚。本课题组前期研究首次发现：1. 生理性结膜分泌主要通过钙激活氯通道（calcium-activated chloride channel，CACC）调控；2. 干眼症中结膜上皮CACC通路可能发生了损害。基于此，我们提出：CACC可能通过调控结膜泪液的分泌并参与干眼症的发生发展。为验证此科学假说，本项目拟建立多种常见的干眼症模型，考察：1. CACC损害是否是各种类型干眼症的共同表现？2.CACC损害的主要环节是什么？3. CACC损害与其他干眼症发病机制之间的关系？和4.干预CACC对泪液分泌的影响？最终回答CACC是否可以作为干眼症治疗的新靶点，并诠释泪液分泌全新的生理病理机制。

泪液分泌稳态破坏会导致干眼症。全球有超十亿人口存在不同程度干眼症。目前其发病机制尚不完全清楚，临床也缺乏很好的治疗手段。最近研究发现结膜分泌占泪液总量的1/4左右，但相关机制及其在干眼症中的确切作用尚不清楚。本课题组前期研究首次发现：1. 生理性结膜分泌主要通过钙激活氯通道（calcium-activated chloride channel，CACC）调控；2. 干眼症中结膜上皮CACC通路可能发生了损害。基于此，我们提出：CACC可能通过调控结膜泪液的分泌并参与干眼症的发生发展。为验证此科学假说，本项目拟建立多种常见的干眼症模型，考察：1. CACC损害是否是各种类型干眼症的共同表现？2.CACC损害的主要环节是什么？3. CACC损害与其他干眼症发病机制之间的关系？和4.干预CACC对泪液分泌的影响？最终回答CACC是否可以作为干眼症治疗的新靶点，并诠释泪液分泌全新的生理病理机制。