ArticleThe American journal of pathology2012
TLR9 ligand CpG-ODN applied to the injured mouse cornea elicits retinal inflammation.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 45 citations in OpenAlex.
- Real-time characterisation of microbe-induced inflammation using a novel zebrafish larval corneal injury and infection model.Communications biology · 2026Article
- CpG-oligodeoxynucleotides challenged macrophages ameliorate acetaminophen induced liver injury by activating TLR9/IRG1/itaconate metabolic pathway.Molecular medicine (Cambridge, Mass.) · 2025Article
- Short chain fatty acids inhibit corneal inflammatory responses to TLR ligands via the ocular G-protein coupled receptor 43.The ocular surface · 2024Article
- Nanoparticle ocular immunotherapy for herpesvirus surface eye infections evaluated in cat infection model.PloS one · 2023Article
- Immune Responses to Gene Editing by Viral and Non-Viral Delivery Vectors Used in Retinal Gene Therapy.Pharmaceutics · 2022Review
- Risk Mitigation of Immunogenicity: A Key to Personalized Retinal Gene Therapy.International journal of molecular sciences · 2021Review
- CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression.Immunology · 2020Article
- Genetic Models of Macrophage Depletion.Methods in molecular biology (Clifton, N.J.) · 2018Review
- Article
- Pleiotropic action of CpG-ODN on endothelium and macrophages attenuates angiogenesis through distinct pathways.Scientific reports · 2016Article
- Retinal glial responses to optic nerve crush are attenuated in Bax-deficient mice and modulated by purinergic signaling pathways.Journal of neuroinflammation · 2016Article
- The role of Toll-like receptors in retinal ischemic diseases.International journal of ophthalmology · 2016Review
- CAPN5 mutation in hereditary uveitis: the R243L mutation increases calpain catalytic activity and triggers intraocular inflammation in a mouse model.Human molecular genetics · 2015Article
- Depletion of CpG Dinucleotides in Papillomaviruses and Polyomaviruses: A Role for Divergent Evolutionary Pressures.PloS one · 2015Article
- Novel Insights on Hantavirus Evolution: The Dichotomy in Evolutionary Pressures Acting on Different Hantavirus Segments.PloS one · 2015Article
- Wounding the cornea to learn how it heals.Experimental eye research · 2014Review
- The Immune System and AMD.Current ophthalmology reports · 2014Article
- Systematic CpT (ApG) depletion and CpG excess are unique genomic signatures of large DNA viruses infecting invertebrates.PloS one · 2014Article
- CpG dinucleotide frequencies reveal the role of host methylation capabilities in parvovirus evolution.Journal of virology · 2013Article
- Host defense at the ocular surface.International reviews of immunology · 2013Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
Abstract
During bacterial and viral infections, unmethylated CpG-DNA released by proliferating and dying microbes is recognized by toll-like receptor (TLR) 9 in host cells, initiating innate immune responses. Many corneal infections occur secondary to epithelial breaches and represent a major cause of vision impairment and blindness globally. To mimic this clinical situation, we investigated mechanisms of TLR9 ligand-induced corneal inflammation in mice after epithelial debridement. Application of CpG oligodeoxynucleotides (ODNs) resulted in neutrophil and macrophage infiltration to the cornea and loss of transparency. By 6 hours after CpG-ODN administration, TLR9 mRNA was increased in the cornea and retina. In vivo clinical examination at 24 hours revealed inflammatory infiltrates in the vitreous and retina, which were confirmed ex vivo to be neutrophils and macrophages, along with activated resident microglia. CpG-ODN-induced intraocular inflammation was abrogated in TLR9(-/-) and macrophage-depleted mice. Bone marrow reconstitution of irradiated TLR9(-/-) mice with TLR9(+/+) bone marrow led to restored corneal inflammatory responses to CpG-ODN. Fluorescein isothiocyanate-CpG-ODN rapidly penetrated the cornea and ocular media to reach the retina, where it was present within CD68(+) retinal macrophages and microglia. These data show that topically applied CpG-ODN induces intraocular inflammation owing to TLR9 activation of monocyte-lineage cells. These novel findings indicate that microbial CpG-DNA released during bacterial and/or viral keratitis can cause widespread inflammation within the eye, including the 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.