ArticleHuman molecular genetics2014
Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 55 citations in OpenAlex.
- Development of an antisense oligonucleotide targeting EFEMP1 in models relevant to macular degeneration.Molecular therapy. Nucleic acids · 2026Article
- Clinical Surrogate Endpoints in Malattia Leventinese/Doyne Honeycomb Retinal Dystrophy: Findings From a Two-Year Natural History Study.Investigative ophthalmology & visual science · 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
- Evaluation of protein profile in vitreous samples of patients with naive age-related macular degeneration using proteomic approaches.BMC geriatrics · 2025Article
- Genetic removal of Nlrp3 protects against age-related and R345W Efemp1-induced basal laminar deposit formation.Cell death & disease · 2025Article
- RPE Basal Lamina Biology and Pathophysiology Related to Age-Related Macular Degeneration.Advances in experimental medicine and biology · 2025Review
- EFEMP1 contributes to light-dependent ocular growth in zebrafish.Biology open · 2024Article
- Exploring ocular fibulin-3 (EFEMP1): Anatomical, age-related, and species perspectives.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Complement factor B is critical for sub-RPE deposit accumulation in a model of Doyne honeycomb retinal dystrophy with features of age-related macular degeneration.Human molecular genetics · 2023Article
- Mouse Choroid Proteome Revisited: Focus on Aging.Advances in experimental medicine and biology · 2023Article
- The extracellular microenvironment in immune dysregulation and inflammation in retinal disorders.Frontiers in immunology · 2023Review
- AMD-Like Substrate Causes Epithelial Mesenchymal Transition in iPSC-Derived Retinal Pigment Epithelial Cells Wild Type but NotInternational journal of molecular sciences · 2021Article
- Complement C5 is not critical for the formation of sub-RPE deposits in Efemp1 mutant mice.Scientific reports · 2021Article
- Measuring the Contributions of Basal Laminar Deposit and Bruch's Membrane in Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2020Article
- Fibulin-3 knockout mice demonstrate corneal dysfunction but maintain normal retinal integrity.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Expression of R345W-Fibulin-3 Induces Epithelial-Mesenchymal Transition in Retinal Pigment Epithelial Cells.Frontiers in cell and developmental biology · 2020Article
- Human complement factor H Y402H polymorphism causes an age-related macular degeneration phenotype and lipoprotein dysregulation in mice.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway.Scientific reports · 2018Article
- Soft Drusen in Age-Related Macular Degeneration: Biology and Targeting Via the Oil Spill Strategies.Investigative ophthalmology & visual science · 2018Review
- Effect of Anti-C5a Therapy in a Murine Model of Early/Intermediate Dry Age-Related Macular Degeneration.Investigative ophthalmology & visual science · 2018Article
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
Abstract
Macular degenerations, inherited and age related, are important causes of vision loss. Human genetic studies have suggested perturbation of the complement system is important in the pathogenesis of age-related macular degeneration. The mechanisms underlying the involvement of the complement system are not understood, although complement and inflammation have been implicated in drusen formation. Drusen are an early clinical hallmark of inherited and age-related forms of macular degeneration. We studied one of the earliest stages of macular degeneration which precedes and leads to the formation of drusen, i.e. the formation of basal deposits. The studies were done using a mouse model of the inherited macular dystrophy Doyne Honeycomb Retinal Dystrophy/Malattia Leventinese (DHRD/ML) which is caused by a p.Arg345Trp mutation in EFEMP1. The hallmark of DHRD/ML is the formation of drusen at an early age, and gene targeted Efemp1(R345W/R345W) mice develop extensive basal deposits. Proteomic analyses of Bruch's membrane/choroid and Bruch's membrane in the Efemp1(R345W/R345W) mice indicate that the basal deposits comprise normal extracellular matrix (ECM) components present in abnormal amounts. The proteomic analyses also identified significant changes in proteins with immune-related function, including complement components, in the diseased tissue samples. Genetic ablation of the complement response via generation of Efemp1(R345W/R345W):C3(-/-) double-mutant mice inhibited the formation of basal deposits. The results demonstrate a critical role for the complement system in basal deposit formation, and suggest that complement-mediated recognition of abnormal ECM may participate in basal deposit formation in DHRD/ML and perhaps other macular degenerations.
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