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Study of the microglia polarity status in diabetic retinophaty in db/db mice

AuthorsArroba, Ana I. ; Cazzoni, Daniele; Hernández, Cristina; Simó, Rafael; Valverde, Ángela M.
Issue Date2014
Citation24th EASDec Meeting (2014)
Abstract[lntroduction]: Retinal diseases linked to inflammation are often accompanied by macrophage/ microglia cells activation. The polarity of microglia may underline their differing functional properties. However, microglia status during Diabetic Retinopathy (DR) has not been investigated and might be useful as a therapeutic target. [Purpose]: Our goal was to study the microglia polarity status during DR in db/db mice, a mouse model of DR. [Methods]: The visual function of db/db mice at 8 and 20 weeks of age has been analysed by ERGs. lmmunofluorescence was used to identify the presence of microglial cells in retina. The polarization of microglia was analysed by measuring the expression of inflammatory markers by western-blot and quantitative PCR (IL6, lL1B, TNF, MCP1, iNOS, Arginase-2). The inflammasome complex was monitored by the activation of caspase-1 by western-blot. [Results]: db/db mice presented a failure in the transmission of post-synaptic wave (bmix response) at the level of retinal ganglion cells, amacrines and horizontal cells at 8 weeks. This effect was due to a failure in the Oscillatory potential response (OP). Moreover, a severe defect in visual function was detected at 20 weeks. At this age, active microglial cells immunopositive for lba-1 marker and resting microglial cells immunopositive for Cd11-b were present in the plexiform layers (OPL, IPL) and the inner nuclear layer (lNL) in db/db mice as compared to db/+ (lean) controls where this response was not observed. Moreover, retinas from 20 weeks-old db/db mice present polarity to M1 response monitored by elevated iNOS, lL-6, lL-1b, MCp1, Arginase-2, reflecting a high pro-inflammatory milieu. [Conclusions]: Our results have demonstrated that microglia is present in the retina and it is polarized towards an immune M1 response at later stages of DR. Therefore, unravelling the progress of microglia polarity in DR offers novel therapeutic interventions.
DescriptionResumen del trabajo presentado al 24th Meeting of the European Association for Study of Diabetes Eye Complications Study Group, celebrado en Padova (Italia) del 15 al 17 de mayo de 2014.
Appears in Collections:(IIBM) Comunicaciones congresos
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