ArticleFrontiers in immunology2017
Bruch's Membrane Compartmentalizes Complement Regulation in the Eye with Implications for Therapeutic Design in Age-Related Macular Degeneration.
Article in Frontiers in immunology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 69 citations in OpenAlex.
- The Biochemical and Genetic Architecture of Geographic Atrophy: The Role of the FHL-1/CFH Axis and the Paradigm of RNA Interference Therapeutics.Biomedicines · 2026Review
- Exploring Endotoxemia in Age-Related Macular Degeneration, Glaucoma, and Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Review
- Pharmacological Characterization of a Novel Complement C3 Inhibitor Antibody Fragment.Ophthalmology and therapy · 2026Article
- Interactions Between Epidermal Growth Factor-Containing Fibulin-Like Extracellular Matrix Protein 1 and Tissue Inhibitor of Metalloproteinases-3 and Relevance to Age-Related Macular Degeneration.Ophthalmology science · 2026Review
- The Promise of Single-Domain Antibodies as Ocular Therapeutics: A Narrative Review.International journal of molecular sciences · 2026Review
- Decoding the Factor H-Related Proteins: Gatekeepers of Complement Dysregulation in AMD.European journal of immunology · 2026Review
- Shifting From Systemic to Precision-Targeted Complement Therapies: Opportunities and Hurdles.European journal of immunology · 2026Review
- Complement in brain and eye disease: shared mechanisms, convergent pathologies, and common therapeutic opportunities.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Review
- CTx001 for Geographic Atrophy: A Gene Therapy Expressing Soluble, Truncated Complement Receptor 1 (Mini-CR1).Ophthalmology science · 2026Article
- Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.Molecular therapy. Methods & clinical development · 2025Article
- From Pathophysiology to Innovative Therapies in Eye Diseases: A Brief Overview.International journal of molecular sciences · 2025Review
- Complement C3/C3aR Signaling Pathway Inhibition Ameliorates Retinal Damage in Experimental Retinal Vein Occlusion.Investigative ophthalmology & visual science · 2025Article
- Metabolomic Characteristics of Aqueous Humor in Wet Age-Related Macular Degeneration and the Impact of Anti-VEGF Treatment.Investigative ophthalmology & visual science · 2025Article
- CFH Haploinsufficiency and Complement Alterations in Early-Onset Macular Degeneration.Investigative ophthalmology & visual science · 2024Article
- The Role of Complement Dysregulation in Glaucoma.International journal of molecular sciences · 2024Review
- Hydroxychloroquine-induced hyperpigmentation of the skin and bull's-eye maculopathy in rheumatic patients: a case report and literature review.Frontiers in immunology · 2024Review
- The complement system in lipid-mediated pathologies.Frontiers in immunology · 2024Review
- Discovery and Potential Utility of a Novel Non-Invasive Ocular Delivery Platform.Pharmaceutics · 2023Article
- AAV Gene Augmentation of Truncated Complement Factor H Differentially Rescues Ocular Complement Dysregulation in a Mouse Model.Investigative ophthalmology & visual science · 2023Article
- Bruch's Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration.Journal of clinical medicine · 2023Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Age-related macular degeneration (AMD) is the leading cause of blindness in the western world and affects nearly 200 million people globally. Local inflammation driven by complement system dysregulation is currently a therapeutic target. Bruch's membrane (BrM) is a sheet of extracellular matrix that separates the retina from the underlying choroid, a highly vascularized layer that supplies oxygen and nutrition to the outer retina. Here, we show that most complement proteins are unable to diffuse through BrM, although FHL-1, factor D and C5a can. AMD-associated lipid deposition in BrM decreases FHL-1 diffusion. We show that this impermeability of BrM creates two separate semi-independent compartments with respect to complement activation and regulation. Complement proteins synthesized locally on either side of BrM, or on the choroidal side if derived from the circulation, predominantly remain on their side of origin. As previous studies suggest that complement activation in AMD is confined to the choroidal side of BrM, we propose a model whereby complement activation in the choriocapillaris layer of the choroid generates C5a, which crosses BrM to interact with its specific receptor on RPE cells to initiate an inflammatory response in the retina. Understanding mechanisms underpinning AMD is essential for developing therapeutics that target the right molecule in the right anatomical compartment.
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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.