The broad-spectrum chemokine inhibitor NR58-3.14.3 modulates macrophage-mediated inflammation in the diseased retina

Journal of Neuroinflammation
Nilisha FernandoMatt Rutar

Abstract

The activity of macrophages is implicated in the progression of retinal pathologies such as atrophic age-related macular degeneration (AMD), where they accumulate among the photoreceptor layer and subretinal space. This process is aided by the local expression of chemokines, which furnish these cells with directional cues that augment their migration to areas of retinal injury. While these qualities make chemokines a potential therapeutic target in curtailing damaging retinal inflammation, their wide variety and signalling redundancy pose challenges in broadly modulating their activity. Here, we examine the efficacy of the broad-spectrum chemokine inhibitor NR58-3.14.3-a suppressor of Ccl- and Cxcl- chemokine pathways-in suppressing macrophage activity and photoreceptor death, using a light-induced model of outer retinal atrophy and inflammation. Photo-oxidative damage was induced in SD rats via exposure to 1000 lux of light for 24 h, after which animals were euthanized at 0- or 7-day post-exposure time points. Prior to damage, NR58-3.14.3 was injected intravitreally. Retinas were harvested and evaluated for the effect of NR58-3.14.3 on subretinal macrophage accumulation and cytokine expression profile, as well as photoreceptor...Continue Reading

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Citations

Mar 14, 2018·PloS One·Nilisha FernandoKrisztina Valter
Mar 27, 2019·Acta Neuropathologica Communications·James F StriebelBruce Chesebro
Jun 16, 2017·Neural Regeneration Research·Ya-Jie WangYu-Hao Li
May 16, 2019·Journal of Nanobiotechnology·Sisi LaiYang Yu
Jul 17, 2020·Frontiers in Cell and Developmental Biology·Nilisha FernandoRiccardo Natoli
Feb 23, 2020·Cell Reports·Kelly MulfaulSarah L Doyle

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Methods Mentioned

BETA
fluorescence-activated cell sorter
PCR
electrophoresis
Fluorescence
FACS

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NIS
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ImageJ
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