El tratamiento de la inflamación en la retina: una nueva estrategia terapéutica en la retinopatía diabética

Resum

Retinal diseases linked to inflammation, including diabetic retinopathy (DR), are often accompanied by resident macrophage/microglial cells activation. During DR, there are substantial changes in the polarization status of the microglia from the M2 (anti-inflammatory) to the M1 (pro-inflammatory) stage. However, the dynamics between M1 and M2 polarization of microglia during DR has not been investigated and it might be therapeutically useful. In this study, we have characterized the evolution of microglia polarizarion during the early stages of DR in the retina of diabetic db/db mice. Moreover, we have analyzed microglia polarization in response to pro- (bacterial lipopolysaccharide; LPS) or anti-(IL4/IL13 cytokines or the bicyclic nojirimycin derivative (1R)-1- dodecylsulfinyl-5N,6O-oxomethylidenenojirimycin (RDS-ONJ)) inflammatory stimuli. For this goal, we have performed in vitro experiments in Bv-2 murine microglial cells as well as ex vivo experiments in retinal explants from db/db mice. Treatment of Bv-2 cells with LPS together with IL4/IL13 or R-DS-ONJ switched the M1 response towards M2. In retinal explants from db/db mice, R-DS-ONJ induced a M2 response. In conclusion, the modulation of microglia polarization dynamics towards a M2 status at early stages of DR offers novel therapeutic interventions