A Perspective of AMD Through the Eyes of Immunology

Copland, David A.; Theodoropoulou, Sofia; Liu, Jian; Dick, Andrew D.

doi:10.1167/iovs.18-23893

Cited by 66Retinal Diseases and TreatmentsOcular Diseases and Behçet’s SyndromeRetinal Imaging and Analysis

A Perspective of AMD Through the Eyes of Immunology

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Copland, David A., Theodoropoulou, Sofia, Liu, Jian, Dick, Andrew D.·2018·Investigative Opthalmology & Visual Science

DOI 10.1167/iovs.18-23893

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Abstract

Despite strong genetic associations, compelling human histological data and numerous hypotheses generated with supportive animal data, the mechanisms of inflammation or inflammatory control of cell health during progression of age-related macular degeneration arguably remain elusive. This perspective delivers a view that maintaining tissue health requires active immune cellular and tissue pathways, but when responses are perturbed or exaggerated, chronic inflammation is destructive. There are potential pathways and processes to enable understanding and determine how potential causative factors including altered cellular metabolism, senescence, oxidative stress disrupt tissue homeostasis are engaged. Establishing differences in the immune phenotype between normal aging and AMD, and how the inter-relatedness of these triggers contribute to pathobiology is integral for future therapeutic success.

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Sustained production of reactive oxygen species, proteases, and inflammatory cytokines can contribute to dysfunction of retinal structures.
“sustained production of reactive oxygen species, proteases, and inflammatory cytokines can contribute to dysfunction of retinal structures [6,201]”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [201]

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Dysregulation in Retinal Para-Inflammation and Age-Related Retinal Degeneration in CCL2 or CCR2 Deficient Mice
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Increased choroidal mast cells and their degranulation in age-related macular degeneration
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New insights into mononuclear phagocyte biology from the visual system
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IL-33 amplifies an innate immune response in the degenerating retina
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Complement factor H binds to denatured rather than to native pentameric C-reactive protein
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“Among the multiple functions ascribed to CRP are activation of the classical complement pathway and inactivation of the AP.49 However, CRP exists in at least two conformational and functionally distinct forms: the native pentameric CRP (pCRP) and a modified/monomeric CRP (mCRP).50,51 The mCRP isoform induces proinflam…”
BackgroundInfluential
Assessing Susceptibility to Age-related Macular Degeneration with Proteomic and Genomic Biomarkers
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Sub-lytic C5b-9 induces functional changes in retinal pigment epithelial cells consistent with age-related macular degeneration
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Complement factor H binding of monomeric C-reactive protein downregulates proinflammatory activity and is impaired with at risk polymorphic CFH variants
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Immune cells in the human choroid
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Protective responses to sublytic complement in the retinal pigment epithelium
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Advances in Age-related Macular Degeneration Understanding and Therapy
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The Role of Complement in Age-Related Macular Degeneration: Heparan Sulphate, a ZIP Code for Complement Factor H?
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Lack of thrombospondin 1 and exacerbation of choroidal neovascularization
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Persistent Inflammation Subverts Thrombospondin-1–Induced Regulation of Retinal Angiogenesis and Is Driven by CCR2 Ligation
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Circulating Autoantibodies in Age-Related Macular Degeneration Recognize Human Macular Tissue Antigens Implicated in Autophagy, Immunomodulation, and Protection from Oxidative Stress and Apoptosis
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Interleukin-17A Induces IL-1β Secretion From RPE Cells Via the NLRP3 Inflammasome
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Beyond VEGF—The Weisenfeld Lecture
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Tissue-Resident Exhausted Effector Memory CD8+ T Cells Accumulate in the Retina during Chronic Experimental Autoimmune Uveoretinitis
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IL-4 Regulates Specific Arg-1+ Macrophage sFlt-1–Mediated Inhibition of Angiogenesis
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Issues with the Specificity of Immunological Reagents for NLRP3: Implications for Age-related Macular Degeneration
Kosmidou, C., Efstathiou, N. E., Hoang, M. V., Notomi, S., Konstantinou, E. K., Hirano, M., Takahashi, K., Maidana, D. E., Tsoka, P., YOUNG, L. H. Y., et al. (2018) · Scientific Reports · doi:10.1038/s41598-017-17634-1 · Cited by 45 · see citing works
Tertiary Lymphoid Tissue Forms in Retinas of Mice with Spontaneous Autoimmune Uveitis and Has Consequences on Visual Function
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Paraquat-Induced Retinal Degeneration Is Exaggerated in CX3CR1-Deficient Mice and Is Associated with Increased Retinal Inflammation
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Authors: Copland, D. A., Theodoropoulou, S., Liu, J., & Dick, A. D.
Affiliations: National Institute for Health and Care Research (GB)
University of Bristol (GB)
Corresponding author: Dick, Andrew D.
ORCID: Copland, David A.
Theodoropoulou, Sofia
Liu, Jian
Dick, Andrew D.
Venue: Investigative Opthalmology & Visual Science
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Published: 2018-07-17
Volume: 59
Issue: 4
Pages: AMD83
ISSN: 0146-0404 (ISSN-L)
1552-5783
DOI: 10.1167/iovs.18-23893
OpenAlex: W2884335216
Cited by: 66
References: 155
Citations by year: 2026: 4 · 2025: 8 · 2024: 8 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 13 · 2019: 3 · 2018: 2
FWCI: 1.24
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by-nc-nd
creativecommons.org/licenses/by-nc-nd/4.0/ (unspecified)
Locations: Investigative Ophthalmology & Visual Science (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Explore Bristol Research (publishedVersion)
UCL Discovery (University College London) (submittedVersion)
Bristol Research (University of Bristol) (submittedVersion)
Funders: National Institute for Health and Care Research (CL-2015-25-502)
Sight Research UK (BRI 008)
Academy of Medical Sciences (SGL017\1042)
Rosetrees Trust (M418-F1)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Retinal Imaging and Analysis
Keywords: age-related macular degeneration, chronic inflammation, immune response, tissue homeostasis, cellular senescence, oxidative stress, cellular metabolism, immunophenotype, aging, pathobiology
MeSH terms: Animals, Humans, Immunity, Cellular, Immunity, Innate, Inflammation, Macular Degeneration, Complement Factor H, Inflammasomes

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A Perspective of AMD Through the Eyes of Immunology

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