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Makoto Inada, Masataka Itou, Masaru Takeuchi; Effects of Dexamethasone on Hypoxia-Induced Retinal Edema. Invest. Ophthalmol. Vis. Sci. 2018;59(9):3206. doi: https://doi.org/.
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Hypoxia is a major cause of retinal edema as well as central nervous system (CNS) edema. These edematous conditions are induced mainly by the dysregulation of blood-tissue barrier.Although dexamethasone (Dex) is used to alleviate CNS edema, the mechanistic detail of its effects on blood-tissue barrier, which is composed of tight-junction of vascular endothelial cells and foot processes of glia cells, has not been elucidated. The aim of this study is to establish mouse model of hypoxia-induced retinal edema and to analyze effects of Dex on this animal model.
8-week-old C57BL6 male mice were divided into four groups; 1) Air-PBS (room air + PBS), 2) Air-Dex (room air + Dex), 3) Hypo-PBS (6% oxygen + PBS), and 4) Hypo-Dex (6% oxygen + Dex). PBS or Dex (16.5μg) injections (i.p.) were followed by room air or 6% oxygen/94% nitrogen exposures in normobaric chamber for 24 hours. After exposures, retinas of the mice of each group were analyzed to observe the gene expressions, vascular permeability, pathological changes, and histological structures.Quantitative real-time PCR was performed to determine the relative expressions of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNFα). Vascular permeability was quantified by Evans-blue dye leakage after air/hypoxic exposure. In addition to standard histological observation by HE staining, immunohistochemical staining for glial fibrillary acidic protein was performed to detect structural changes in glial cells. Ultrastructural changes were observed by transmission electron microscope with nitrate lanthanum as a tracer.
VEGF and TNFα expressions in retina were significantly up-regulated in Hypo-PBS group (p<0.05), and the up-regulations in both VEGF and TNFα in Hypo-Dex group were alleviated to the level of Air-PBS group. Vascular permeability was significantly increased in Hypo-PBS group (p<0.05) and that was relieved in Hypo-Dex group. Edematous changes were found at nerve fiber layer in Hypo-PBS group. Electron microscopic observation showed swollen glial foot processes around capillaries and tight-junction disruptions in the vascular endothelial cells in Hypo-PBS group.
Mouse model of hypoxia-induced retinal edema was established. Dex alleviated hypoxia-induced retinal edema though preservation of blood-retinal barrier function, preventing VEGF and TNFα up-regulations.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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