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Ana I. Arroba, Ángela M. Valverde
levels of pro-inflammatory cytokines remained similar as p38 MAPK: p38 Mitogen-activated Protein Kinase
in age-matched db+ lean mice. However, the analysis of qRT-PCR: quantitative Real-Time PCR
M1/M2 markers in total retina revealed the coexistence of RNA: Ribonucleic Acid
elevated iNOS (M1) and arginase-1 (M2) mRNA and RPE: Retinal Pigment Epithelium
protein levels only at an early stage of DR (5 weeks), both SEM: Standar error of the Mean
markers being localized mainly in the IPL, OPL and GCL
where microglia was immunodetected. By contrast, in 7. CONFLICT OF INTEREST
retinas of db/db mice at 8 weeks both the decrease in
arginase-1 and the maintenance of high expression of The authors declare that there is no conflict of interest
iNOS paralleled the IL6 and TNFa mRNA levels. Taken associated with this manuscript.
together, these data indicate that in the retina of db/db
mice the loss of the anti-inflammatory defense correlated 8. ACKNOWLEDGMENTS
with deterioration of the visual function in an age-
dependent manner (20). Importantly, in retinas from db/db We acknowledge Drs EM. Sánchez-Fernández, C.
mice at 8 weeks treatment with R-DS-ONJ reduced GFAP Ortiz Mellet and JM. García Fernández (University of
immunostaining and also increased arginase-1, reflecting a Sevilla, Spain) for supplying C5. This work was supported
regression towards an early stage of DR. by grants from the Spanish Ministry of Economy and
Competitivity (SAF2015-65267-R and SAF2012-33283),
This study also provides new mechanistic insights in an in Comunidad de Madrid S2010/BMD-2423 and
vitro bioassay that mimics the pro-inflammatory context of S2010/BMD2439, Centro de Investigación Biomédica en
DR. We have used LPS as a pro-inflammatory stimulus in Red de Diabetes y Enfermedades Metabólicas Asociadas
Bv-2 mouse microglia cell line since the M1 response of (CIBERdem, Instituto Carlos III, Spain), European Union
these cells resembles the in vivo situation in db/db mice in (EUROCONDOR (FP7 HEALTH.2011.2.4.3.1.)).
the course of DR. In Bv-2 microglial cells treated with
LPS, the co-treatment with IL4/IL3 (M2 cytokines) or the 9. REFERENCES
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@Real Academia Nacional de Farmacia. Spain
