ArticleJournal of neuroinflammation2020
An allosteric interleukin-1 receptor modulator mitigates inflammation and photoreceptor toxicity in a model of retinal degeneration.
Article in Journal of neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Integrated meta-analysis of human astrocytes transcriptomes reveals a candidate recurrent inflammatory signature in response to inflammatory and immune stimuli.Frontiers in cellular neuroscience · 2026Pooled it
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- The role of IGF2BP2 in macrophage-mediated NLRP3 inflammasome activation in the pathogenesis of dry AMD.Biology direct · 2025Article
- Priming and release of cytokine IL-1β in microglial cells from the retina.Experimental eye research · 2025Article
- Induction, amplification, and propagation of diabetic retinopathy-associated inflammatory cytokines between human retinal microvascular endothelial and Müller cells and in the mouse retina.Cellular signalling · 2024Article
- Age-Related Choroidal Involution Is Associated with the Senescence of Endothelial Progenitor Cells in the Choroid.Biomedicines · 2024Article
- Retinal perivascular macrophages regulate immune cell infiltration during neuroinflammation in mouse models of ocular disease.The Journal of clinical investigation · 2024Article
- Suppression of inner blood-retinal barrier breakdown and pathogenic Müller glia activation in ischemia retinopathy by myeloid cell depletion.Journal of neuroinflammation · 2024Article
- Single-cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy.Clinical and translational medicine · 2024Review
- Predicting Preterm Birth Using Proteomics.Clinics in perinatology · 2024Review
- Addressing a broken drug pipeline for preterm birth: why early preterm birth is an orphan disease.American journal of obstetrics and gynecology · 2023Article
- Impairing Gasdermin D-mediated pyroptosis is protective against retinal degeneration.Journal of neuroinflammation · 2023Article
- Overview of Caffeine Effects on Human Health and Emerging Delivery Strategies.Pharmaceuticals (Basel, Switzerland) · 2023Review
- FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration.Journal of neuroinflammation · 2022Article
- The Therapeutic Prospects of Targeting IL-1R1 for the Modulation of Neuroinflammation in Central Nervous System Disorders.International journal of molecular sciences · 2022Review
- Gene-agnostic therapeutic approaches for inherited retinal degenerations.Frontiers in molecular neuroscience · 2022Review
- Landscape of Preterm Birth Therapeutics and a Path Forward.Journal of clinical medicine · 2021Review
- Role of innate inflammation in traumatic brain injury.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021Review
- Caffeine Protects Against Retinal Inflammation.Frontiers in pharmacology · 2021Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundInflammation and particularly interleukin-1β (IL-1β), a pro-inflammatory cytokine highly secreted by activated immune cells during early AMD pathological events, contribute significantly to retinal neurodegeneration. Here, we identify specific cell types that generate IL-1β and harbor the IL-1 receptor (IL-1R) and pharmacologically validate IL-1β's contribution to neuro-retinal degeneration using the IL-1R allosteric modulator composed of the amino acid sequence rytvela (as well as the orthosteric antagonist, Kineret) in a model of blue light-induced retinal degeneration.
methodsMice were exposed to blue light for 6 h and sacrificed 3 days later. Mice were intraperitoneally injected with rytvela, Kineret, or vehicle twice daily for 3 days. The inflammatory markers F4/80, NLRP3, caspase-1, and IL-1β were assessed in the retinas. Single-cell RNA sequencing was used to determine the cell-specific expression patterns of retinal Il1b and Il1r1. Macrophage-induced photoreceptor death was assessed ex vivo using retinal explants co-cultured with LPS-activated bone marrow-derived macrophages. Photoreceptor cell death was evaluated by the TUNEL assay. Retinal function was assessed by flash electroretinography.
resultsBlue light markedly increased the mononuclear phagocyte recruitment and levels of inflammatory markers associated with photoreceptor death. Co-localization of NLRP3, caspase-1, and IL-1β with F4/80
conclusionThese findings substantiate the importance of IL-1β in neuro-retinal degeneration and revealed specific sources of Il1b from perivascular MPs, with its receptor Ilr1 being separately expressed on surrounding neuro-vascular and astroglial cells. They also validate the efficacy of rytvela-induced IL-1R modulation in suppressing detrimental inflammatory responses and preserving photoreceptor density and function in these conditions, reinforcing the rationale for clinical translation.
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Registered trials
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