ArticleThe Journal of clinical investigation2023
Early-life peripheral infections reprogram retinal microglia and aggravate neovascular age-related macular degeneration in later life.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Artesunate ameliorates experimental autoimmune uveitis by inhibiting the LCN2-STAT3 axis and suppressing microglial activation.Redox report : communications in free radical research · 2026Article
- Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Review
- Genetic context alters central nervous system compartment dependent responses to lipopolysaccharide.bioRxiv : the preprint server for biology · 2026Article
- Vitreoretinal Myeloid Cell Heterogeneity: Diverse Roles in Homeostasis, Immune Surveillance, and Pathophysiology.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Low-grade peripheral inflammation accelerates retinal amyloid pathology and dysfunction in an Alzheimer's disease mouse model.Acta neuropathologica communications · 2026Article
- Dual-Target ROS-Driven Spatiotemporal Senolysis for Vascular Repair and Immune Microenvironment Reprogramming in the Treatment of Ocular Fundus Neovascularization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Rethinking Neonatal Vaccination Policies: A Neuroimmune Perspective.Iranian journal of medical sciences · 2026Review
- Article
- Heterochronic parabiosis uncovers AdipoR1 as a critical player in retinal rejuvenation.Science advances · 2025Article
- Immune Checkpoint PD-L1 Modulates Retinal Microglial Activation to Alleviate Vascular Leakage in Choroidal Neovascularization via ERK.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Features that distinguish age-related macular degeneration from aging.Experimental eye research · 2025Review
- Vitamin K1 Alleviates Retinal Inflammation Following Acute Ocular Hypertension by Modulating Microglial Ferroptosis.Investigative ophthalmology & visual science · 2025Article
- Article
- Complement proteins and complement regulatory proteins are associated with age-related macular degeneration stage and treatment response.Journal of neuroinflammation · 2024Article
- Differential Effect of Aldosterone or Mineralocorticoid Receptor Overexpression on Retinal Inflammation.Investigative ophthalmology & visual science · 2024Article
- Revamping anti-cGAS-STING therapy via an injectable thermo-responsive supramolecular hydrogel for pathological retinal angiogenesis.Asian journal of pharmaceutical sciences · 2024Article
- Sensory Dysfunction, Microbial Infections, and Host Responses in Alzheimer's Disease.The Journal of infectious diseases · 2024Review
- Ocular and Serum Profiles of Inflammatory Molecules Associated With Retinitis Pigmentosa.Translational vision science & technology · 2024Article
- Decoding cellular plasticity and niche regulation of limbal stem cells during corneal wound healing.Stem cell research & therapy · 2024Article
- Decoding physiological and pathological roles of innate immune cells in eye diseases: the perspectives from single-cell RNA sequencing.Frontiers in immunology · 2024Review
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pathological neovascularization in age-related macular degeneration (nvAMD) drives the principal cause of blindness in the elderly. While there is a robust genetic association between genes of innate immunity and AMD, genome-to-phenome relationships are low, suggesting a critical contribution of environmental triggers of disease. Possible insight comes from the observation that a past history of infection with pathogens such as Chlamydia pneumoniae, or other systemic inflammation, can predispose to nvAMD in later life. Using a mouse model of nvAMD with prior C. pneumoniae infection, endotoxin exposure, and genetic ablation of distinct immune cell populations, we demonstrated that peripheral infections elicited epigenetic reprogramming that led to a persistent memory state in retinal CX3CR1+ mononuclear phagocytes (MNPs). The immune imprinting persisted long after the initial inflammation had subsided and ultimately exacerbated choroidal neovascularization in a model of nvAMD. Single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) identified activating transcription factor 3 (ATF3) as a central mediator of retina-resident MNP reprogramming following peripheral inflammation. ATF3 polarized MNPs toward a reparative phenotype biased toward production of proangiogenic factors in response to subsequent injury. Therefore, a past history of bacterial endotoxin-induced inflammation can lead to immunological reprograming within CNS-resident MNPs and aggravate pathological angiogenesis in the aging retina.
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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.