ArticleScientific reports2017
Fractalkine-CX3CR1 signaling is critical for progesterone-mediated neuroprotection in the retina.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 55 citations in OpenAlex.
- Neurosteroid (3α,5α)3-hydroxypregnan-20-one enhancement of anti-inflammatory chemokine CX3CL1 exhibits sex, brain region, and cellular specificity in alcohol-preferring rats.Psychopharmacology · 2026Article
- Targeting the CCL7-STAT1 axis attenuates microglial neurotoxicity and photoreceptor degeneration in retinitis pigmentosa.Journal of neuroinflammation · 2026Article
- Exploring retinal microglia: development, degeneration, and iPSC-derived model systems.Brain structure & function · 2026Review
- Single-Cell RNA-Seq Reveals Aging-Related Impairment of Microglial Efferocytosis Contributing to Apoptotic Cells Accumulation After Retinal Injury.Aging cell · 2025Article
- Glial Cell Responses and Gene Expression Dynamics in Retinas of Treated and Untreated RPE65 Mutant Dogs.Investigative ophthalmology & visual science · 2024Article
- Neurosteroid [3α,5α]-3-Hydroxy-pregnan-20-one Enhances the CX3CL1-CX3CR1 Pathway in the Brain of Alcohol-Preferring Rats with Sex-Specificity.Life (Basel, Switzerland) · 2024Article
- Immunology of Retinitis Pigmentosa and Gene Therapy-Associated Uveitis.Cold Spring Harbor perspectives in medicine · 2024Review
- Sialic Acid Mimetic Microglial Sialic Acid-Binding Immunoglobulin-like Lectin Agonism: Potential to Restore Retinal Homeostasis and Regain Visual Function in Age-Related Macular Degeneration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Soluble CX3CL1-expressing retinal pigment epithelium cells protect rod photoreceptors in a mouse model of retinitis pigmentosa.Stem cell research & therapy · 2023Article
- Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy.Frontiers in molecular neuroscience · 2023Review
- Age-dependent changes on fractalkine forms and their contribution to neurodegenerative diseases.Frontiers in molecular neuroscience · 2023Review
- Differential distribution of steroid hormone signaling networks in the human choroid-retinal pigment epithelial complex.BMC ophthalmology · 2022Article
- Neuroinflammation in retinitis pigmentosa: Therapies targeting the innate immune system.Frontiers in immunology · 2022Review
- More than meets the eye: The role of microglia in healthy and diseased retina.Frontiers in immunology · 2022Review
- Association of CX3CL1 and CX3CR1 Expression with Liver Fibrosis in a Mouse Model of Schistosomiasis.Current medical science · 2020Article
- The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders.Current neuropharmacology · 2020Review
- Selective Histone Deacetylase 6 Inhibitors Restore Cone Photoreceptor Vision or Outer Segment Morphology in Zebrafish and Mouse Models of Retinal Blindness.Frontiers in cell and developmental biology · 2020Article
- Microglia in Retinal Degeneration.Frontiers in immunology · 2019Review
- IP3-Mediated Calcium Signaling Is Involved in the Mechanism of Fractalkine-Induced Hyperalgesia Response.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- Neuroprotective strategies for retinal disease.Progress in retinal and eye research · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina. Norgestrel upregulates fractalkine-CX3CR1 signaling in the rd10 retina, coinciding with photoreceptor survival. We show that Norgestrel-treated photoreceptor-like cells, 661Ws, and C57 explants modulate rd10 microglial activity in co-culture, resulting in increased photoreceptor survival. Assessment of Norgestrel's neuroprotective effects when fractalkine was knocked-down in 661 W cells and release of fractalkine was reduced in rd10 explants confirms a crucial role for fractalkine-CX3CR1 signaling in Norgestrel-mediated neuroprotection. To further understand the role of fractalkine in neuroprotection, we assessed the release of 40 cytokines in fractalkine-treated rd10 microglia and explants. In both cases, treatment with fractalkine reduced a variety of pro-inflammatory cytokines. These findings further our understanding of Norgestrel's neuroprotective properties, capable of modulating harmful microglial activity indirectly through photoreceptors, leading to increased neuroprotection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.