期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
卷 1862, 期 9, 页码 1663-1674出版社
ELSEVIER
DOI: 10.1016/j.bbadis.2016.05.024
关键词
Diabetic retinopathy; Microglia; Inflammation
资金
- Spanish Ministry of Economy and Competitivity [SAF2015-65267-R, SAF2012-35562, SAF2013-44021-R]
- Junta de Andalucia [FQM2012-1467]
- Comunidad de Madrid [S2010/BMD-2423, S2010/BMD2439]
- Institute de Salud Carlos III [PI13-02098]
- Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERdem, Institute Carlos III, Spain)
- Red de Patologia Ocular Prevalente y Cronica (OFTARED, Institute de Salud Carlos III, Spain)
- European Union (EUROCONDOR) [FP7 HEALTH.2011.2.4.3.1]
- European Union Seventh Framework Programme [333594]
Retinal diseases linked to inflammation are often accompanied by macrophage/microglial cells activation. However, the dynamics between M1 (pro-inflammatory) and M2 (anti-inflammatory) polarization of microglia during diabetic retinopathy (DR) has not been investigated and it might be therapeutically useful. We assessed microglia polarization in retinas from db/db mice and human diabetic donors and also the microglia-mediated anti-inflammatory effects of the bicyclic nojirimycin derivative (1R)-1-dodecylsulfinyl-5N,6O-oxomethylidenenojirimycin (R-DS-ONJ). Visual function in mice was evaluated by electroretinogram (ERG). Expression of pro- and anti-inflammatory markers in the retina was analyzed by immunofluorescence, Western-blot and quantitative real-time PCR. Lipopolysaccharide (LPS)-mediated polarization profile was studied in Bv.2 microglial cells in the absence or presence of anti-inflammatory cytokines (IL4/IL13) or R-DS-ONJ. At 5 weeks of age, reduced ERG amplitude values of rod and mixed waves were detected in db/db compared to db/+ mice that correlated with elevated circulating endotoxemia and pro-inflammatory cytokines. At this early stage of DR, the marker of activated microglia lba-1 co-localized with the M2 marker arginase-1 in the retina. Conversely, in retinas from 8 weeks old db/db mice Iba-l-colocalized with active caspase-1, a key component of the inflammasome, reflecting an opposite pattern of microglia polarization. Markers of activated microglia were detected in retinas of diabetic donors. Treatment of Bv.2 cells with LPS and 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. (C) 2016 Elsevier B.V. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据