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  • Conjunctival Fluid Secretion Impairment via CaCC-CFTR Dysfunction Is the Key Mechanism in Environmental Dry Eye.

Conjunctival Fluid Secretion Impairment via CaCC-CFTR Dysfunction Is the Key Mechanism in Environmental Dry Eye.

International journal of molecular sciences (2022-11-27)
Jinyu Zhang, Limian Lin, Xiaomin Chen, Shuyi Wang, Yuan Wei, Wenliang Zhou, Shuangjian Yang, Shiyou Zhou
ABSTRACT

Dry eye disease (DED) is a multifactorial disease with an incidence of approximately 50% worldwide. DED seriously affects quality of life and work. The prevalence of environmental DED (eDED) ranges from 35 to 48%. Conjunctival fluid secretion dysfunction may be one of the major causes of DED. Notably, the Cl- flux corresponds to the conjunctival fluid secretion and could be affected by ATP. Both the cystic fibrosis transmembrane conductance regulator (CFTR) and the Ca2+-activated Cl- channel (CaCC) are Cl- channels involved in epithelial fluid secretion. Conjunctival fluid secretion could be increased by activating P2Y2R (an ATP receptor) in DED. However, the role of the CaCC and CFTR channels regulated by P2Y2R in eDED remains unclear. In this study, we established a rabbit eDED model using a controlled drying system. A Ussing chamber was used to perform a conjunctival short-circuit current induced by ATP to evaluate the reactivity of the ion channels to the ATP. Our results revealed that eDED accompanied by conjunctival fluid secretion impairment was caused by a P2Y2R dysfunction, which is related to CaCC-CFTR signaling in the conjunctiva epithelium. Notably, the coupling effect of the ATP-induced CaCC-CFTR activation and intracellular Ca2+ may represent a promising therapeutic target for treating eDED.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
U-73122 hydrate, powder
Sigma-Aldrich
2-APB, A cell-permeable modulator of Ins(1,4,5)P3-induced Ca2+ release.
Sigma-Aldrich
T16Ainh-A01, ≥95% (HPLC)
Sigma-Aldrich
BAPTA-AM, ≥95% (HPLC)
Sigma-Aldrich
H-89 dihydrochloride hydrate, ≥98% (HPLC), powder