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On phagocytes and macular degeneration
Open accessAbstract
Age related macular degeneration (AMD) is a complex multifactorial disease caused by the interplay of age and genetic and environmental risk factors. A common feature observed in early and both forms of late AMD is the breakdown of the physiologically immunosuppressive subretinal environment and the protracted accumulation of mononuclear phagocytes (MP). We here discuss the origin and nature of subretinal MPs, the mechanisms that lead to their accumulation, the inflammatory mediators they produce as well as the consequences of their chronic presence on photoreceptors, retinal pigment epithelium and choroid. Recent advances highlight how both genetic and environmental risk factors directly promote subretinal inflammation and tip the balance from a beneficial inflammation that helps control debris accumulation to detrimental chronic inflammation and destructive late AMD. Finally, we discuss how changes in life style or pharmacological intervention can help to break the vicious cycle of inflammation and degeneration, restore the immunosuppressive properties of the subretinal space, and reestablish homeostasis.
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“Beyond the participation of mononuclear phagocytes and the innate immune response in AMD (6), a few clinical investigations also con fi rmed other systemic immune pro fi le alterations in T cell frequencies in AMD patients (7).”
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“However, animal studies and donor eyes from patients with GA have revealed that the BRB does not seem to be an obstacle for circulating cells to enter the retina (Guillonneau et al., 2017; Sennlaub et al., 2013).”
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“27 Candidate cells suspected of containing such hyperreflective substances include ectopic RPE cells 21,23,27–31 and mononuclear phagocytes, 24,25,32–38 including resident microglia and recruited inflammatory macrophages that ingest and retain RPE organelles.”
BackgroundComplement-mediated release of fibroblast growth factor 2 from human RPE cells
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Potential gene identification and pathway crosstalk analysis of age-related macular degeneration
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“These atypical appearances of monocytes can be explained by a combination of abnormal signaling receptor binding, including age-related increase of CCL2, deficiency of CX3CL1 as well as proinflammatory pattern of interleukins (Guillonneau et al., 2017).”
BackgroundPoor Response to Bevacizumab Correlates With Higher IL-6 and IL-8 Aqueous Cytokines in AMD
Connolly, E., El-Farouki, G., Brennan, K., Cahill, M. T., & Doyle, S. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.11.37 · Cited by 9
“24,25 28 IL-17 is known to promote VEGF-mediated angiogenesis by enhancing VEGF-induced growth of vascular endothelial cells, 29 and it has been shown that IL-17 can stimulate exacerbation of neovascularization in a VEGF-independent manner.”
Tarallo, V., Trotta, S. M., Panico, S., D’Orsi, L., Mercadante, G., Cicatiello, V., & Falco, S. D. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.8.12 · Cited by 5
Long Term Time-Lapse Imaging of Geographic Atrophy: A Pilot Study
Pâques, M., Norberg, N., Chaumette, C., Sennlaub, F., Rossi, E. A., Borella, Y., & Grieve, K. F. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2022.868163 · Cited by 5
“The fact that hyperreflective spots show mobilization is rather unsurprising since such motion of intraretinal cells has already been shown in vivo (29); it may be related to the fact that macrophages, which are migrating in response to inflammatory stimuli, are present in eyes affected by GA and may contain melanin f…”
BackgroundSelf-citationBorella, Y., Danielsen, N., Markle, E. M., Snyder, V. C., Lee, D. M. W., Zhang, M., Eller, A. W., Chhablani, J. K., Pâques, M., & Rossi, E. A. (2024) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.65.10.28 · Cited by 5
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RetractedMacrophage/microglia-dependent mechanisms drive retinal pigment epithelium regeneration in zebrafish
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“5,38 One could expect that lowered vagal function would cause a decrease in circulating anti-inflammatory immune cells.”
Self-citationChoroidal macrophages in homeostasis, aging and age-related macular degeneration
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Self-citationMacular fibrosis secondary to neovascular age-related macular degeneration: from clinic to biology
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Lamp2 Deficiency Enhances Susceptibility to Oxidative Stress–Induced RPE Degeneration
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“49,50 These monocytes initially express high levels of Ly6C, which gradually decrease as they differentiate into macrophages.”
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Non-Coding RNAs: Novel Regulators of Macrophage Homeostasis in Ocular Vascular Diseases
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BackgroundPten Loss Triggers Progressive Photoreceptor Degeneration in an mTORC1-Independent Manner
Hanna, J., Touahri, Y., Pak, A., David, L. A., van Oosten, E., Dixit, R., Vecchio, L. M., Mehta, D. N., Minamisono, R., Aubert, I., et al. (2025) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.66.3.45 · Cited by 1
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CXCR4+ monocytes promote neovascularization in wet age-related macular degeneration
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InfluentialAging of the retinal pigment epithelium
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“A shared pathogenic axis across AMD forms is chronic inflammation (Guillonneau et al., 2017; Yu et al., 2020).”
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Development of safe and efficient aav vectors for retinal gene therapy
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Maladie de Parkinson et DMLA : y a-t-il un lien ?
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Le promoteur du gène SLC16A8, une cible thérapeutique pour la Dégénérescence Maculaire liée à l'âge
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Adipocytes influence choroidal neovascularization via PRDM16
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Infiltrating monocyte fate switch in retinal degeneration: from early pathology to late homeostasis
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Metadata
- Authors
- Guillonneau, X., Eandi, C. M., Paques, M., Sahel, J.-A., Sapieha, P., & Sennlaub, F.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- University of Turin (IT)
- Hôpital Maisonneuve-Rosemont (CA)
- Corresponding author
- Sennlaub, Florian
- Venue
- Progress in Retinal and Eye Research
- Publisher
- Elsevier BV
- Published
- 2017-11
- Volume
- 61
- Pages
- 98-128
- ISSN
- 1350-9462 (ISSN-L)
- OpenAlex
- W2622806731
- Cited by
- 185
- References
- 399
- Citations by year
- 2026: 13 · 2025: 15 · 2024: 31 · 2023: 16 · 2022: 19 · 2021: 33 · 2020: 20 · 2019: 19 · 2018: 18 · 2017: 1
- FWCI
- 2.91
- Type
- journal article
- Language
- en
- Open access
- Licence
- Locations
- Progress in Retinal and Eye Research (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion, other-oa)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- INSERM
- ANR Geno 2009 (R09099DS)
- ANR MACLEAR (ANR-15-CE14-0015-01)
- LABEX LIFESENSES (ANR-10-LABX-65)
- ANR (Investissements d'Avenir programme (ANR-11-IDEX-0004-02)
- Carnot
- ERC (ERC-2007 St.G. 210345)
- Association de Prévoyance Santé de ALLIANZ
- Topics
- Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
- Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
- Health Sciences › Medicine › Ophthalmology › Retinal Development and Disorders
- Keywords
- age-related macular degeneration, mononuclear phagocytes, chronic inflammation, retinal pigment epithelium, photoreceptors, choroid, genetic risk factors, environmental risk factors, immunosuppression, lifestyle modification
- MeSH terms
- Choroid, Humans, Life Style, Macular Degeneration, Macular Edema, Phagocytes, Photoreceptor Cells, Retinal Pigment Epithelium
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