Sökning: WFRF:(Lachota Mieszko)
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NF-kappa B activati...
NF-kappa B activation in retinal microglia is involved in the inflammatory and neovascularization signaling in laser-induced choroidal neovascularization
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- Hikage, Fumihito (författare)
- Sapporo Med Univ, Japan
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- Lennikov, Anton (författare)
- Univ Missouri, MO USA; Harvard Med Sch, MA 02115 USA
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- Mukwaya, Anthonny (författare)
- Linköpings universitet,Avdelningen för sinnesorgan och kommunikation,Medicinska fakulteten
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- Lachota, Mieszko (författare)
- Med Univ Warsaw, Poland
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- Ida, Yosuke (författare)
- Sapporo Med Univ, Japan
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- Utheim, Tor Paaske (författare)
- Oslo Univ Hosp, Norway; Oslo Univ Hosp, Norway
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- Chen, Dong Feng (författare)
- Harvard Med Sch, MA 02115 USA
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- Huang, Hu (författare)
- Univ Missouri, MO USA
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- Ohguro, Hiroshi (författare)
- Sapporo Med Univ, Japan
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(creator_code:org_t)
- ELSEVIER INC, 2021
- 2021
- Engelska.
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Ingår i: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 403:1
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Purpose: To evaluate Nuclear Factor NF-kappa B (NF-kappa B) signaling on microglia activation, migration, and angiogenesis in laser-induced choroidal neovascularization (CNV). Methods: Nine-week-old C57BL/6 male mice were randomly assigned to IMD-0354 treated or untreated groups (5 mice, 10 eyes per group). CNV was induced with a 532-nm laser. Laser spots (power 250 mW, spot size 100 mu m, time of exposure 50 ms) were created in each eye using a slit-lamp delivery system. Selective inhibitor of nuclear factor kappa-B kinase subunit beta (IKK2) inhibitor IMD-0354 (10 mu g) was delivered subconjunctivally; vehicle-treated mice were the control. The treatment effect on CNV development was assessed at five days post-CNV induction in vivo in C57BL/6 and Cx3cr1(gfp/wt) mice by fluorescent angiography, fundus imaging, and ex vivo by retinal flatmounts immunostaining and Western blot analysis of RPE/Choroidal/Scleral complexes (RCSC) lysates. In vitro evaluations of IMD-0354 effects were performed in the BV-2 microglial cell line using lipopolysaccharide (LPS) stimulation. Results: IMD-0354 caused a significant reduction in the fluorescein leakage and size of the laser spot, as well as a reduction in microglial cell migration and suppression of phospho-I kappa B alpha, Vascular endothelial growth factor (VEGF-A), and Prostaglandin-endoperoxide synthase 2 (COX-2). In vivo and ex vivo observations demonstrated reduced lesion size in mice, CD68, and Allograft inflammatory factor 1 (IBA-1) positive microglia cells migration to the laser injury site in IMD-0354 treated eyes. The data further corroborate with GFP-positive cells infiltration of the CNV site in Cx3cr1(wt/gfp) mice. In vitro IMD-0354 (10-25 ng/ml) treatment reduced NF-kappa B activation, expression of COX-2, caused decreased Actin-F presence and organization, resulting in reduced BV-2 cells migration capacity. Conclusion: The present data indicate that NF-kappa B activation in microglia and its migration capacity is involved in the development of laser CNV in mice. Its suppression by NF-kappa B inhibition might be a promising therapeutic strategy for wet AMD.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Laser CNV; Retina; IKK-beta; IKK2; NF-kappa B; Microglia; IMD-0354
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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