Chief Supervisor

Prof. ZHOU Lei

Project Title

S100A8/A9 as a therapeutic target in dry eye disease 

Synopsis

S100A8 and S100A9 proteins both belong to small calcium-binding dimeric proteins with high structural homology and pleiotropic functions. These proteins are constitutively expressed in myeloid-derived cells including neutrophils and monocytes and are induced in macrophages. Actually, they have complicated phenotypes that may suggest their different roles in different kinds of pathologic processes. For example, S100A8/A9 complex, the most common existent heterodimer, known as calprotectin, can suppress acute inflammation and has antimicrobial activities. 

Dry eye disease (DED), defined by the Tear Film and Ocular Society (TFOS) in the Dry Eye Workshop II (DEWS II) report, is a multifactorial disease of the ocular surface defined by the disruption of homeostasis of the tear film. The ocular signs accompanying DED are tear film instability and hyperosmolarity, ocular surface inflammation and damage, and neurosensory abnormalities. DED patients have some symptoms such as dryness, itching, redness, visual disturbance, and ocular fatigue. All these uncomfortable ocular problems can considerably affect individuals’ daily life and work. In some severe cases, it can even instigate mood alterations and depression. Currently, there has been increasing research on developing effective and safe ocular drugs for the treatment of dry eye disease. 

Studies focused on the identification of tear biomarkers of ocular surface diseases have shown that S100A8 and S100A9 proteins have important roles in inflammatory and immune processes. Hence, we aim to investigate the impact of S100A8/A9 phenotypes on the pathologic process in dry eye disease. Based on our findings, we will choose the inhibitors of these phenotypes to investigate the specific treatment of dry eye disease.