Targeting purinergic receptors to attenuate inflammation of dry eye

Inflammation is one of the potential factors to cause the damage of ocular surface in dry eye disease (DED). Increasing evidence indicated that purinergic A₁, A_2A, A₃, P2X4, P2X7, P2Y₁, P2Y₂, and P2Y₄ receptors play an important role in the regulation of inflammation in DED: A₁ adenosine receptor (A_1R) is a systemic pro-inflammatory factor; A_2AR is involved in the activation of the MAPK/NF-kB pathway; A_3R combined with inhibition of adenylate cyclase and regulation of the mitogen-activated protein kinase (MAPK) pathway leads to regulation of transcription; P2X4 promotes receptor-associated activation of pro-inflammatory cytokines and inflammatory vesicles; P2X7 promotes inflammasome activation and release of pro-inflammatory cytokines IL-1β and IL-18; P2Y receptors affect the phospholipase C(PLC)/IP3/Ca²⁺ signaling pathway and mucin secretion. These suggested that purinergic receptors would be promising targets to control the inflammation of DED in the future.