ArticleThe Journal of biological chemistry2015
Complement Component C5a Primes Retinal Pigment Epithelial Cells for Inflammasome Activation by Lipofuscin-mediated Photooxidative Damage.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 69 citations in OpenAlex.
- Avacincaptad pegol for geographic atrophy secondary to age-related macular degeneration: 18-month findings from the GATHER1 trial.Eye (London, England) · 2023Trial
- Murine models of neovascular AMD revisited: Mechanistic pathways, immune-metabolic crosstalk, and the impact of aging and sex.Experimental eye research · 2026Review
- Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Review
- The role of NLRP3 inflammasome in age-related macular degeneration: mechanisms and therapeutic prospects.Frontiers in aging neuroscience · 2026Review
- Aqueous humour extracellular vesicle membrane protein profiling reveals pathological features of refractory macular edema.Frontiers in cell and developmental biology · 2026Article
- Follow the Molecule from Crystal Arthropathy to Comorbidities: The 2024 G-CAN Gold Medal Award Awardee Lecture.Gout, urate, and crystal deposition disease · 2025Article
- C5a-Induced Autophagy Dysfunction Promotes Choroidal Neovascularization Through the ROS-Inflammatory Pathway.Investigative ophthalmology & visual science · 2025Article
- Complement C5a promotes human retinal pigment epithelial cell viability and migration through SLC38A1-mediated glutamine metabolism.Medical microbiology and immunology · 2025Article
- Article
- C3aR1-Deletion Delays Retinal Degeneration in a White-Light Damage Mouse Model.Investigative ophthalmology & visual science · 2025Article
- One-Year Outcomes in Subjects Developing Macular Neovascularization While Undergoing Avacincaptad Pegol Therapy for Geographic Atrophy.Clinical ophthalmology (Auckland, N.Z.) · 2025Article
- The Complement System as a Therapeutic Target in Retinal Disease.Medicina (Kaunas, Lithuania) · 2024Review
- Real-World Outcomes in Pre-Existing Neovascular Age-Related Macular Degeneration Subjects Undergoing Avacincaptad Therapy for Geographic Atrophy.Clinical ophthalmology (Auckland, N.Z.) · 2024Article
- Review
- Neural-Cardiac Inflammasome Axis after Traumatic Brain Injury.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Qihuang Granule protects the retinal pigment epithelium from oxidative stress via regulation of the alternative complement pathway.BMC complementary medicine and therapies · 2023Article
- Autophagy in age-related macular degeneration.Autophagy · 2023Review
- Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells.Frontiers in immunology · 2023Article
- FoxP3 expression by retinal pigment epithelial cells: transcription factor with potential relevance for the pathology of age-related macular degeneration.Journal of neuroinflammation · 2022Article
- Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Complement activation, oxidative damage, and activation of the NLRP3 inflammasome have been implicated in retinal pigment epithelium (RPE) pathology in age-related macular degeneration (AMD). Following priming of RPE cells, the NLRP3 inflammasome can be activated by various stimuli such as lipofuscin-mediated photooxidative damage to lysosomal membranes. We investigated whether products of complement activation are capable of providing the priming signal for inflammasome activation in RPE cells. We found that incubation of primary human RPE cells and ARPE-19 cells with complement-competent human serum resulted in up-regulation of C5a receptor, but not C3a receptor. Furthermore, human serum induced expression of pro-IL-1β and enabled IL-1β secretion in response to lipofuscin phototoxicity, thus indicating inflammasome priming. Complement heat-inactivation, C5 depletion, and C5a receptor inhibition suppressed the priming effect of human serum whereas recombinant C5a likewise induced priming. Conditioned medium of inflammasome-activated RPE cells provided an additional priming effect that was mediated by the IL-1 receptor. These results identify complement activation product C5a as a priming signal for RPE cells that allows for subsequent inflammasome activation by stimuli such as lipofuscin-mediated photooxidative damage. This molecular pathway provides a functional link between key factors of AMD pathogenesis including lipofuscin accumulation, photooxidative damage, complement activation, and RPE degeneration and may provide novel therapeutic targets in this disease.
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