ArticleScientific reports2016
Connecting the innate and adaptive immune responses in mouse choroidal neovascularization via the anaphylatoxin C5a and γδT-cells.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 64 citations in OpenAlex.
- Exploring Biomarkers and Mechanisms of Action of Adaptive Immune Response in Age-Related Macular Degeneration Based on Transcriptomics.Biomedicines · 2026Article
- Associations between the monocyte‑lymphocyte ratio and age‑related macular degeneration among US adults: evidence from NHANES 2005-2008.International journal of retina and vitreous · 2025Article
- Artemisinin and Its Derivatives: Promising Therapeutic Agents for Age-Related Macular Degeneration.Pharmaceuticals (Basel, Switzerland) · 2025Review
- High Levels of C5a Are Associated With Reduced Macular Sensitivity in Patients With Myeloproliferative Neoplasms.Investigative ophthalmology & visual science · 2025Article
- Rac1 overexpression promotes Treg-derived cytokines to mediate choroidal neovascularization in wet age-related macular degeneration.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Associations of the Adaptive Immune System and Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- Aryl hydrocarbon receptor (AhR)-mediated immune responses to degeneration of the retinal pigment epithelium.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Unveiling the role of NK cells, NKT-like cells, and γδ cells in pathogenesis of type 1 reactions in leprosy.Heliyon · 2024Article
- Corneal application of SOCS1/3 peptides for the treatment of eye diseases mediated by inflammation and oxidative stress.Frontiers in immunology · 2024Review
- Protective role of IL-17-producing γδ T cells in a laser-induced choroidal neovascularization mouse model.Journal of neuroinflammation · 2023Article
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
- Innate immune biology in age-related macular degeneration.Frontiers in cell and developmental biology · 2023Review
- Suppressor of cytokine signaling 3-derived peptide as a therapeutic for inflammatory and oxidative stress-induced damage to the retina.Molecular vision · 2023Article
- Evaluation of a connexin-based peptide for the treatment of age-related macular degeneration.Heliyon · 2022Article
- The role of the adaptive immune system and T cell dysfunction in neurodegenerative diseases.Journal of neuroinflammation · 2022Review
- Dabigatran and Wet AMD, Results From Retinal Pigment Epithelial Cell Monolayers, the Mouse Model of Choroidal Neovascularization, and Patients From the Medicare Data Base.Frontiers in immunology · 2022Article
- Cytokine Profiles and the Effect of Intravitreal Aflibercept Treatment on Experimental Choroidal Neovascularization.Ophthalmic research · 2022Article
- Potential gene identification and pathway crosstalk analysis of age-related macular degeneration.Frontiers in genetics · 2022Article
- Peptide-based immunotherapy against oxidized elastin ameliorates pathology in mouse model of smoke-induced ocular injury.Experimental eye research · 2021Article
- Natural immunoglobulin M-based delivery of a complement alternative pathway inhibitor in mouse models of retinal degeneration.Experimental eye research · 2021Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Neovascular age-related macular degeneration (AMD) is characterized by choroidal neovascularization (CNV). An overactive complement system is associated with AMD pathogenesis, and serum pro-inflammatory cytokines, including IL-17, are elevated in AMD patients. IL-17 is produced by complement C5a-receptor-expressing T-cells. In murine CNV, infiltrating γδT- rather than Th17-cells produce the IL-17 measurable in lesioned eyes. Here we asked whether C5a generated locally in response to CNV recruits IL-17-producing T-cells to the eye. CNV lesions were generated using laser photocoagulation and quantified by imaging; T-lymphocytes were characterized by QRT-PCR. CNV resulted in an increase in splenic IL-17-producing γδT- and Th17-cells; yet in the CNV eye, only elevated levels of γδT-cells were observed. Systemic administration of anti-C5- or anti-C5a-blocking antibodies blunted the CNV-induced production of splenic Th17- and γδT-cells, reduced CNV size and eliminated ocular γδT-cell infiltration. In ARPE-19 cell monolayers, IL-17 triggered a pro-inflammatory state; and splenocyte proliferation was elevated in response to ocular proteins. Thus, we demonstrated that CNV lesions trigger a systemic immune response, augmenting local ocular inflammation via the infiltration of IL-17-producing γδT-cells, which are presumably recruited to the eye in a C5a-dependent manner. Understanding the complexity of complement-mediated pathological mechanisms will aid in the development of an AMD treatment.
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