ArticleCell death & disease2022
IL-4 induces reparative phenotype of RPE cells and protects against retinal neurodegeneration via Nrf2 activation.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
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- INflammatory MediatorS in the PathophysIology of Diabetic REtinopathy Study: Baseline Analysis of 24 Aqueous Cytokines.Ophthalmology science · 2026Article
- Characterization and biocompatibility evaluation of a Ti@HA-GO@IL-4 bioactive composite coating for guided bone regeneration in dental implant applications.BMC oral health · 2025Article
- Intermittent fasting attenuates glial hyperactivation and photoreceptor degeneration in a NaIOCommunications biology · 2025Article
- Targeting RPE Senescence Via Suppressing IL-6/IL-6R Signaling for Treating Retinal Degenerative Diseases.Investigative ophthalmology & visual science · 2025Article
- AAV2.7m8 transduction of stage 2 human retinal organoids induces highly variable responses in innate and inflammatory gene expression and cytokine secretion.Experimental eye research · 2025Article
- Platelet-Released Growth Factors (PRGFs) Activate NRF2-ARE and Modulate Inflammatory Response in an NRF2-Dependent Manner in Primary Human Keratinocytes.Journal of cosmetic dermatology · 2025Article
- Mosla Chinensis Extract Enhances Growth Performance, Antioxidant Capacity, and Intestinal Health in Broilers by Modulating Gut Microbiota.Microorganisms · 2024Article
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- Variations in inflammatory regulators in male patients with chronic schizophrenia associated with psychopathology and cognitive deficits.BMC psychiatry · 2024Article
- IL-23 Priming Enhances the Neuroprotective Effects of MSC-Derived Exosomes in Treating Retinal Degeneration.Investigative ophthalmology & visual science · 2024Article
- Therapeutic intervention in neuroinflammation for neovascular ocular diseases through targeting the cGAS-STING-necroptosis pathway.Journal of neuroinflammation · 2024Article
- NLRP3 and autophagy in retinal ganglion cell inflammation in age-related macular degeneration: potential therapeutic implications.International journal of ophthalmology · 2024Review
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Retinal degeneration is a kind of neurodegeneration characterized by progressive neuronal death and dysfunction of retinal pigment epithelium (RPE) cells, leading to permanent visual impairment. It still lacks effective therapeutic options and new drugs are highly warranted. In this study, we found the expression of IL-4, a critical regulator of immunity, was reduced in both patients and mouse models. Importantly, exogenous intravitreal IL-4 application could exert a novel neuroprotective effect, characterized by well-preserved RPE layer and neuroretinal structure, as well as amplified wave-amplitudes in ERG. The RNA-seq analysis revealed that IL-4 treatment suppressed the essential oxidative and pro-inflammatory pathways in the degenerative retina. Particularly, IL-4 upregulated the IL-4Rα on RPE cells and induced a reparative phenotype via the activation of Nrf2 both in vitro and in vivo. Furthermore, the Nrf2-/- mice displayed no recovery in response to IL-4 application, highlighting a significant role of Nrf2 in IL-4-mediated protection. Our data provides evidence that IL-4 protects against retinal neurodegeneration by its antioxidant and anti-inflammatory property through IL-4Rα upregulation and Nrf2 activation in RPE cells. The IL-4/IL-4Rα-Nrf2 axis maybe the potential targets for the development of novel therapies for neurodegenerative diseases.
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