Purpose

Damaged cells release high levels of extracellular ATP, which constitutes a potent danger signal. The purinergic receptor P2X7 is the main sensor of high amounts of ATP and its activation triggers an inflammatory response and/or induces cell death. In uveitis, P2X7 may contribute to the development of retinal damage via its expression on immune cells. Given the multiple functions of P2X7, its activation could play distinct roles in the development of the disease depending on the cell type that expresses it. We investigated the function of P2X7 in mouse experimental autoimmune uveitis (EAU) using new conditional P2X7 knockout mouse strains.

Methods

The effects of P2X7 modulation were analyzed using multidisciplinary approaches. EAU scoring was performed in vivo by fundoscopic exam. The number and the phenotype of the different immune cell subpopulations were analyzed by flow cytometry in the lymph nodes, the spleen and the retina.

Results

Our data showed that P2X7 is expressed in the different immune cell subpopulations in the retina during EAU. While we did not find any significant effect of total P2X7 invalidation, the severity of EAU was significantly reduced when P2X7 was specifically depleted in retinal microglia/mononuclear phagocytes.

Conclusions

Thus, targeted inhibition of P2X7 could be a promising therapeutic approach for the treatment of uveitis.