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Activation of retinal microglia and accumulation of sub‐retinal fluid after systemic challenge with Lipopolysaccharide in mice
Author(s) -
Kokona D.,
Ebneter A.,
Zinkernagel M.
Publication year - 2017
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2017.02331
Subject(s) - microglia , retinal , lipopolysaccharide , retina , blood–retinal barrier , retinal degeneration , inflammation , retinal disorder , fluorescein angiography , medicine , immunology , pathology , chemistry , biology , endocrinology , diabetic retinopathy , ophthalmology , neuroscience , diabetes mellitus
Purpose Retinal pathology such as diabetic retinopathy can be exacerbated by systemic viral illness. However, little is known whether systemic inflammation causes activation of retinal microglia. The aim of the present study was to investigate the effect of a systemic inflammatory stimulus with lipopolysaccharide ( LPS ) on retinal microglia activation. Methods LPS (1 mg/kg) was administered intravenously for 4 days in Cx3cr1gfp/+ mice, specifically expressing gfp in microglia/macrophages. Retinas were examined with optical coherence tomography, fluorescein angiography and autofluorescence imaging before and after the LPS challenge. A group of mice was fed with the colony stimulating factor‐1 receptor ( CSF ‐1R) inhibitor PLX 5622, which has been shown to deplete retinal microglia after 48 hours, for 7 days and until the end of the experiments. PLX ‐fed mice were challenged with LPS as above, imaged and euthanized at day 4 of the LPS challenge. Results Accumulation of sub‐retinal fluid and leakage of fluorescein was observed in the retinas of LPS mice, suggesting disruption of the blood retinal barrier ( BRB ). In vivo imaging and histology showed increased numbers of gfp+ cells in retinas and brains and accumulation around retinal vessels in the LPS group. Increase of gfp+ cell numbers was partially attributed to proliferation, based on Ki67 staining. PLX attenuated the numbers of gfp+ cells and reversed the effects of LPS on sub‐retinal fluid accumulation. Conclusions Our data suggest that systemic LPS challenge initiates inflammatory responses in the retina and can lead to disruption of the BRB , whose integrity seems to be highly dependent on retinal microglia and/or invading macrophages. Pathology is completely abrogated in microglia depleted mice, suggesting that novel CSF ‐1R inhibitors may be a promising target for inflammation mediated retinal diseases.