Subretinal mononuclear phagocytes induce cone segment loss via IL-1β

Chiara M. Eandi (1, 2) , Hugo Charles-Messance (1) , Sébastien Augustin (1) , Elisa Dominguez (1) , Sophie Lavalette (1) , Valérie Forster (1) , Shulong Justin Hu (1) , Lourdes Siquieros (1) , Cheryl Mae Craft (3, 4) , José-Alain Sahel (5, 1) , Ramin Tadayoni (6, 1) , Michel Paques (1, 5) , Xavier Guillonneau (1) , Florian Sennlaub (1)

1 Institut de la Vision
2 UNITO - Università degli studi di Torino = University of Turin
3 UCLA - University of California [Los Angeles]
4 Keck School of Medicine [Los Angeles]
5 CHNO - Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts
6 Service d'ophthalmologie [CHU Lariboisière]

Photo-transduction in cone segments (CS) is crucial for high acuity daytime vision. For ill-defined reasons, CS degenerate in retinitis pigmentosa (RP) and in the transitional zone (TZ) of atrophic zones (AZ), which characterize geographic atrophy (GA). Our experiments confirm the loss of cone segments (CS) in the TZ of patients with GA and show their association with subretinal CD14+mononuclear phagocyte (MP) infiltration that is also reported in RP. Using human and mouse MPs in vitro and inflammation-prone Cx3cr1GFP/GFPmice in vivo, we demonstrate that MP-derived IL-1β leads to severe CS degeneration. Our results strongly suggest that subretinal MP accumulation participates in the observed pathological photoreceptor changes in these diseases. Inhibiting subretinal MP accumulation or Il-1β might protect the CS and help preserve high acuity daytime vision in conditions characterized by subretinal inflammation, such as AMD and RP.

Domaines: Organes des sens

Chiara M. Eandi, Hugo Charles-Messance, Sébastien Augustin, Elisa Dominguez, Sophie Lavalette, et al.. Subretinal mononuclear phagocytes induce cone segment loss via IL-1β. eLife, 2016, 5, pp.e16490. ⟨10.7554/eLife.16490⟩. ⟨hal-01365291⟩