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N. N. Vagaja, N. Binz, E. P. Rakoczy, P. G. McMenamin; The Response of the Retina to Systemic Inflammatory Stimuli in a Model of Background Non-Proliferative Diabetic Retinopathy. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5613.
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© ARVO (1962-2015); The Authors (2016-present)
It has been proposed that some of the pathological changes in background diabetic retinopathy [DR] (neuronal loss, endothelial cell death, leukostasis, microglial changes and VEGF fluctuations) may represent evidence of low grade inflammation. In light of emerging evidence that systemic inflammatory events alter the progression of neurodegenerative disorders, we postulate that an acute episode of systemic inflammation may accelerate pathological changes in a spontaneous mouse model of non-proliferative DR.
Male 6-7 week old Akita mice (hyperglycaemic from week 4 onwards) and wild- type (WT) littermates were given a single intraperitoneal injection of either ultra pure E. coli LPS (9µg/g body weight) or sterile saline (PBS). At 24 hours endothelial cell death and leukostasis were evaluated in retinal wholemounts after in vivo staining with propidium iodide, followed one hour later by perfusion with fluorescent con A and fixative. Retinal microglial phenotype (CD11b, F4/80, MHC-II, CD169) was studied by confocal microscopy. Quantitative analysis of VEGF protein (Luminex) and mRNA (real time PCR) was also performed. Samples from 6-8 animals/group were used for each study.
24h after LPS, WT mice demonstrated increased venular leukostasis (p<0.0001) and mild capillary endothelial damage (p< 0.001) compared to PBS controls. In LPS-treated Akita mice the leukostasis was less marked (p<0.01) than in LPS-treated WT but there was increased endothelial cell damage (p<0.01). Following LPS exposure, microglia in Akita mice showed increased expression of CD11b and altered morphology. LPS exposure caused a slight drop in VEGF mRNA and protein in WT retinae but not in Akita mice.
A single episode of systemic inflammation in diabetic mice resulted in changes in retinal vasculature and retinal microglia, together with altered patterns of VEGF production. The data presented lends tentative support to the hypothesis that systemic inflammation might exaggerate the pathogenetic processes in background DR.
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