☆ 4.6 Review

Age-related macular degeneration: A disease of extracellular complement amplification

IMMUNOLOGICAL REVIEWS (2023)

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Article Oncology

Local factor H production by human choroidal endothelial cells mitigates complement deposition: implications for macular degeneration

Kelly Mulfaul et al.

Summary: Activation of the alternative complement pathway is a crucial event in the development of age-related macular degeneration (AMD). Uncontrolled complement activation leads to the formation of the membrane attack complex (MAC). This study demonstrates that reduced levels of complement factor H (FH) in the choroid can contribute to MAC deposition on choroidal endothelial cells (CECs), while overexpression of FH can protect against MAC deposition. These findings highlight the importance of local FH production in preventing MAC deposition in AMD.

JOURNAL OF PATHOLOGY (2022)

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Article Ophthalmology

Progression of Age-Related Macular Degeneration Among Individuals Homozygous for Risk Alleles on Chromosome 1 (CFH-CFHR5) or Chromosome 10 (ARMS2/HTRA1) or Both

Steffen Schmitz-Valckenberg et al.

Summary: The study investigated the specific associations of the 2 most common genetic risk loci for AMD and found that these loci have differential effects on disease progression, possibly involving distinct biological mechanisms.

JAMA OPHTHALMOLOGY (2022)

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Article Biochemistry & Molecular Biology

Systemic complement levels in patients with age-related macular degeneration carrying rare or low-frequency variants in the CFH gene

Sarah de Jong et al.

Summary: Age-related macular degeneration (AMD) is a common cause of vision loss in elderly individuals in the Western world. Genetic variants in the CFH gene have been associated with AMD, leading to decreased FH levels and increased C3bBbP levels in carriers. Understanding the effects of rare CFH gene variants can improve clinical interpretation of AMD patients.

HUMAN MOLECULAR GENETICS (2022)

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Article Ophthalmology

New approaches to the treatment of Age-Related Macular Degeneration (AMD)

Karl Csaky et al.

EXPERIMENTAL EYE RESEARCH (2022)

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Article Biotechnology & Applied Microbiology

The Human Eye Transcriptome Atlas: A searchable comparative transcriptome database for healthy and diseased human eye tissue

Julian Wolf et al.

Summary: This study developed a web-based transcriptome database that allows for easy exploration and comparison of ocular gene expression in healthy and diseased human ocular tissues without requiring bioinformatics expertise. By analyzing gene expression in 100 ocular tissue samples, the researchers identified tissue-specific genes and cellular profiles. The database provides rapid access to detailed insights into the molecular mechanisms of various ocular tissues and diseases, as well as potential new diagnostic and therapeutic targets.

GENOMICS (2022)

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Article Multidisciplinary Sciences

Mast cell infiltration of the choroid and protease release are early events in age-related macular degeneration associated with genetic risk at both chromosomes 1q32 and 10q26

Selina Mcharg et al.

Summary: Age-related macular degeneration (AMD) is a major cause of visual loss and is strongly associated with common haplotypes on chromosome 1 (CFH Y402H variant) and chromosome 10 (near HTRA1/ARMS2). In this study, the submacular tissue of older donors with genetic risk but without clinical features of AMD was analyzed using mass spectrometry-based quantitative proteomics. The results showed that the high-risk allele groups on chromosome 1 and chromosome 10 had common protein changes compared to the low-risk group, particularly increased levels of mast cell-specific proteases. Additional histological analyses revealed increased mast cells and denatured collagen in the submacular tissue of donors with genetic risk of AMD but without clinical features, as well as in donors with high-risk chromosome 1 alleles and early AMD. These findings suggest that increased mast cell infiltration, degranulation, and extracellular matrix remodeling are early events in AMD pathogenesis, and represent a mechanistic link between chromosome 1 and chromosome 10-mediated AMD.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

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Article Multidisciplinary Sciences

The crystal structure of iC3b-CR3 αI reveals a modular recognition of the main opsonin iC3b by the CR3 integrin receptor

Francisco J. Fernandez et al.

Summary: This study reveals the structural basis of the interaction between human opsonin iC3b and the von Willebrand A inserted domain of the alpha chain of CR3, providing insights into complement activation and pathogen clearance by macrophages.

NATURE COMMUNICATIONS (2022)

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Article Immunology

Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation

Alexandra Papp et al.

Summary: Components of the extracellular matrix (ECM) are found to be associated with complement activation and inflammation, while the proteins FHR1 and FHR5 are implicated in renal and eye diseases. It has been discovered that FHR1 and FHR5 can bind to specific ECM components, affecting the activity of complement inhibitor FH and promoting complement activation.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Immunology

As in Real Estate, Location Matters: Cellular Expression of Complement Varies Between Macular and Peripheral Regions of the Retina and Supporting Tissues

Randy Zauhar et al.

Summary: This study investigates the complement pathway in ocular degeneration, particularly age-related macular degeneration (AMD). The findings reveal that the cellular response to AMD is more robust in the choroid during early stages and more prominent in the retina during late stages. Additionally, the cooperation of different cell types plays a significant role in complement expression.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Cell Biology

Transcriptional comparison of adult human primary Retinal Pigment Epithelium, human pluripotent stem cell-derived Retinal Pigment Epithelium, and ARPE19 cells

Elke K. Markert et al.

Summary: This study examines the mature state and characteristics of RPE cells derived from different sources. The results show that induced pluripotent stem cell-derived RPE cells are more similar to adult primary RPE cells in terms of gene expression and characteristics, while the ARPE-19 line is different. The study also finds that iPSC-RPE cells are more sensitive to epithelial-mesenchymal transition and aggregate formation compared to ahRPE cells.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2022)

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Article Medicine, General & Internal

Genetic Variants of Complement Factor H Y402H (rs1061170), C2 R102G (rs2230199), and C3 E318D (rs9332739) and Response to Intravitreal Anti-VEGF Treatment in Patients with Exudative Age-Related Macular Degeneration

Agnieszka Kubicka-Trzaska et al.

Summary: This study assessed the association between single nucleotide polymorphisms (SNPs) in the CFH, C2, and C3 genes and response to anti-VEGF therapy in patients with exudative AMD. The CC genotype of the CFH gene was associated with AMD and poor response to therapy. On the other hand, carriers of the TT genotype showed better response to therapy.

MEDICINA-LITHUANIA (2022)

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Article Ophthalmology

Evaluating a Causal Relationship between Complement Factor I Protein Level and Advanced Age-Related Macular Degeneration Using Mendelian Randomization

Amy Jones et al.

Summary: This study investigates the relationship between rare genetic variants and complement factor I (CFI) levels, as well as the association between CFI levels and risk of advanced age-related macular degeneration (AAMD). The study finds that low circulating CFI levels are associated with an increased risk of AAMD, and provides genetic evidence to support this relationship.

OPHTHALMOLOGY SCIENCE (2022)

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Article Ophthalmology

C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration A Randomized Pivotal Phase 2/3 Trial

Glenn J. Jaffe et al.

Summary: The study evaluated the safety and efficacy of the C5 inhibitor avacincaptad pegol in patients with geographic atrophy secondary to age-related macular degeneration. Results showed a significant reduction in the growth rate of GA and good tolerability after 12 months of treatment.

OPHTHALMOLOGY (2021)

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Review Biotechnology & Applied Microbiology

Current Clinical Applications of In Vivo Gene Therapy with AAVs

Jerry R. Mendell et al.

Summary: Hereditary diseases are caused by gene mutations, affecting millions of Americans, and gene therapy using adeno-associated virus (AAV) has shown promise in treating these diseases. Five treatments have been approved for commercialization, with many more in clinical trials, showcasing the potential of gene therapy in treating a wide range of genetic disorders.

MOLECULAR THERAPY (2021)

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Review Ophthalmology

Implications of genetic variation in the complement system in age-related macular degeneration

Sarah de Jong et al.

Summary: AMD is a major cause of vision loss in elderly individuals in the Western world. The complement system plays a crucial role in disease risk associated with AMD. Despite ongoing research on complement inhibitors in clinical trials, the success has been limited, leaving many AMD patients without effective treatment options.

PROGRESS IN RETINAL AND EYE RESEARCH (2021)

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Article Multidisciplinary Sciences

Epithelial phenotype restoring drugs suppress macular degeneration phenotypes in an iPSC model

Ruchi Sharma et al.

Summary: This study presents an in vitro iPSC-RPE model for AMD that replicates drusen and RPE atrophy, and identifies two drugs that reduce deposits and restore RPE phenotype. The findings provide molecular insights into the role of CFH(H/H) risk-allele in AMD and discover two candidate drugs for AMD treatment.

NATURE COMMUNICATIONS (2021)

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Article Immunology

Interleukin-33 Amplifies Human Mast Cell Activities Induced by Complement Anaphylatoxins

Peter W. West et al.

Summary: Aberrant mast cell responses and complement activation both contribute to allergic diseases. IL-33 plays a critical role in regulating mast cell responses to complement anaphylatoxins, enhancing mast cell reactivity to C3a and C5a. This cross-regulation may aggravate Th2 immune responses and targeting anti-IL33 therapeutically could provide a rationale in allergic diseases.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Immunology

Complement Factor H-Related 3 Enhanced Inflammation and Complement Activation in Human RPE Cells

Nicole Schaefer et al.

Summary: FHR-3 binds oxidative stress epitopes and competes with FH, modulating complement components and receptors expression of RPE cells, inducing inflammation and activating cytokine secretion.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Biochemistry & Molecular Biology

The rare C9 P167S risk variant for age-related macular degeneration increases polymerization of the terminal component of the complement cascade

O. McMahon et al.

Summary: Age-related macular degeneration is a complex neurodegenerative eye disease leading to irreversible vision loss among elderly Caucasians. Genetic variants in the complement pathway play a significant role in the disease, with the rare C9 P167S variant associated with low plasma levels of C9 and increased polymerization and hemolytic activity. This finding provides a basis for gene therapy trials targeting the terminal pathway of complement in AMD.

HUMAN MOLECULAR GENETICS (2021)

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Article Biochemistry & Molecular Biology

Complement Factor H Loss in RPE Cells Causes Retinal Degeneration in a Human RPE-Porcine Retinal Explant Co-Culture Model

Angela Armento et al.

Summary: The study utilizing a co-culture model demonstrated the detrimental effects of FH loss in RPE cells on the retina, with observed changes in mitochondrial and lipid composition. The model is applicable not only to porcine retinal explants but also to human retinal explants, providing valuable insights for AMD research.

BIOMOLECULES (2021)

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Article Cell Biology

Impaired Mitochondrial Function in iPSC-Retinal Pigment Epithelium with the Complement Factor H Polymorphism for Age-Related Macular Degeneration

Mara C. Ebeling et al.

Summary: The study investigated the impact of donor disease state and genotype on mitochondrial function and inflammation in RPE cells derived from donors with or without AMD. Cells from donors with AMD showed decreased mitochondrial function and increased inflammatory markers. CFH high-risk cells exhibited a more pronounced reduction in mitochondrial function and increased inflammatory markers, regardless of disease state.

CELLS (2021)

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Article Genetics & Heredity

Beyond factor H: The impact of genetic-risk variants for age-related macular degeneration on circulating factor-H-like 1 and factor-H-related protein concentrations

Valentina Cipriani et al.

Summary: The study revealed that mutations at the complement factor H (CFH) locus may lead to elevated concentrations of circulating FHR proteins, which could be major drivers of AMD. These findings support the need for research into FHR protein modulation as a potential therapeutic avenue for AMD.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

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Article Genetics & Heredity

Common haplotypes at the CFH locus and low-frequency variants in CFHR2 and CFHR5 associate with systemic FHR concentrations and age-related macular degeneration

Laura Lores-Motta et al.

Summary: FHR proteins were identified as key players in the AMD disease mechanism, suggesting that therapies targeting specific individuals with AMD based on their genotypes at the CFH locus could be effective.

AMERICAN JOURNAL OF HUMAN GENETICS (2021)

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Article Hematology

Functional characterization of 105 factor H variants associated with aHUS: lessons for variant classification

Hector Martin Merinero et al.

Summary: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy mainly caused by pathogenic variants in genes encoding complement components and regulators. Accurate classification of FH gene CFH variants remains challenging due to lack of functional studies, emphasizing the importance of functional assays in interpreting FH variants.

BLOOD (2021)

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Review Biochemistry & Molecular Biology

A look into retinal organoids: methods, analytical techniques, and applications

Tess A. V. Afanasyeva et al.

Summary: In the era of personalized medicine, induced pluripotent stem cells (iPSCs) have emerged as a valuable system for cell replacement and modeling of inherited retinal diseases (IRDs). Three-dimensional iPSCs-derived retinal organoids containing various retinal cell types show promise for advancing research and treatments for IRDs.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

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Article Biochemistry & Molecular Biology

Complement Factor B Mediates Ocular Angiogenesis through Regulating the VEGF Signaling Pathway

Hannah Murray et al.

Summary: CFB is a crucial catalytic element in the alternative pathway of complement, playing a key role in ocular angiogenesis by promoting blood vessel formation through mediating the VEGF signaling pathway. This study provides compelling evidence for the involvement of CFB in driving ocular neovascularization in a VEGF-dependent manner, suggesting potential therapeutic targets for blinding eye diseases characterized by pathological angiogenesis.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2021)

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Article Multidisciplinary Sciences

FHL-1 interacts with human RPE cells through the α5β1 integrin and confers protection against oxidative stress

Rawshan Choudhury et al.

Summary: The study revealed a non-canonical role of FHL-1 in protecting RPE cells against oxidative stress and identified a novel interaction with implications for ocular diseases such as age-related macular degeneration.

SCIENTIFIC REPORTS (2021)

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Article Biochemical Research Methods

Microfluidic organ-on-a-chip model of the outer blood-retinal barrier with clinically relevant read-outs for tissue permeability and vascular structure

Yusuf B. Arik et al.

Summary: Researchers have developed a microfluidic organ-on-a-chip model to simulate the outer blood-retinal barrier, containing a monolayer of immortalized human RPE cells and a microvessel of human endothelial cells separated by a semi-permeable membrane. This model can mimic the effects of oxidative stress on barrier permeability and provide clinically relevant endpoints for studying complex disease mechanisms and treatments for visual disorders in vitro.

LAB ON A CHIP (2021)

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Article Ophthalmology

Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration A Randomized Phase 2 Trial

David S. Liao et al.

OPHTHALMOLOGY (2020)

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Review Ophthalmology

Interactions of the choroid, Bruch's membrane, retinal pigment epithelium, and neurosensory retina collaborate to form the outer blood-retinal-barrier

Mark A. Fields et al.

PROGRESS IN RETINAL AND EYE RESEARCH (2020)

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Review Biochemistry & Molecular Biology

The role of lymphocytes and phagocytes in age-related macular degeneration (AMD)

Verena Behnke et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2020)

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Article Biochemistry & Molecular Biology

Basement membrane ligands initiate distinct signalling networks to direct cell shape

Michael J. Randles et al.

MATRIX BIOLOGY (2020)

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Review Ophthalmology

The cell biology of the retinal pigment epithelium

Aparna Lakkaraju et al.

PROGRESS IN RETINAL AND EYE RESEARCH (2020)

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Article Multidisciplinary Sciences

Increased circulating levels of Factor H-Related Protein 4 are strongly associated with age-related macular degeneration

Valentina Cipriani et al.

NATURE COMMUNICATIONS (2020)

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Article Cell & Tissue Engineering

Stem cell-derived retinal pigment epithelium from patients with age-related macular degeneration exhibit reduced metabolism and matrix interactions

Jie Gong et al.

STEM CELLS TRANSLATIONAL MEDICINE (2020)

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Review Pathology

Complement Membrane Attack Complex New Roles, Mechanisms of Action, and Therapeutic Targets

Catherine B. Xie et al.

AMERICAN JOURNAL OF PATHOLOGY (2020)

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Article Biochemistry & Molecular Biology

A role for mast cells in geographic atrophy

Shuntaro Ogura et al.

FASEB JOURNAL (2020)

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Article Biochemistry & Molecular Biology

Effect of rare coding variants in the CFI gene on Factor I expression levels

Sarah de Jong et al.

HUMAN MOLECULAR GENETICS (2020)

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Article Immunology

Interaction of the Factor H Family Proteins FHR-1 and FHR-5 With DNA and Dead Cells: Implications for the Regulation of Complement Activation and Opsonization

Eva Karpati et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Clinical Neurology

APOE and dementia - resequencing and genotyping in 105,597 individuals

Katrine L. Rasmussen et al.

ALZHEIMERS & DEMENTIA (2020)

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Cell Types of the Human Retina and Its Organoids at Single-Cell Resolution

Cameron S. Cowan et al.

CELL (2020)

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Article Ophthalmology

Integrating Metabolomics, Genomics, and Disease Pathways in Age-Related Macular Degeneration The EYE-RISK Consortium

Ilhan E. Acar et al.

OPHTHALMOLOGY (2020)

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Loss of Complement Factor H impairs antioxidant capacity and energy metabolism of human RPE cells

Angela Armento et al.

SCIENTIFIC REPORTS (2020)

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Review Biochemistry & Molecular Biology

Matrix Metalloproteinases in Age-Related Macular Degeneration (AMD)

Luis Garcia-Onrubia et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

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Review Immunology

Tuning the Functionality by Splicing: Factor H and Its Alternative Splice Variant FHL-1 Share a Gene but Not All Functions

Marco Mannes et al.

FRONTIERS IN IMMUNOLOGY (2020)

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Article Ophthalmology

Functional Analysis of Rare Genetic Variants in Complement Factor I (CFI) using a Serum-Based Assay in Advanced Age-related Macular Degeneration

Anuja Java et al.

TRANSLATIONAL VISION SCIENCE & TECHNOLOGY (2020)

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Article Biochemistry & Molecular Biology

Properdin Modulates Complement Component Production in Stressed Human Primary Retinal Pigment Epithelium Cells

Nicole Schaefer et al.

ANTIOXIDANTS (2020)

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Article Ophthalmology

Complement Activation in the Vitreous of Patients With Proliferative Diabetic Retinopathy

Nikhil Mandava et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2020)

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Article Ophthalmology

Complement factors and reticular pseudodrusen in intermediate age-related macular degeneration staged by multimodal imaging

Anne M. Lynch et al.

BMJ OPEN OPHTHALMOLOGY (2020)

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Article Ophthalmology

Geographic Atrophy: Confocal Scanning Laser Ophthalmoscopy, Histology, and Inflammation in the Region of Expanding Lesions

Vera L. Bonilha et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2020)

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Article Ophthalmology

Rare Genetic Variants in Complement Factor I Lead to Low FI Plasma Levels Resulting in Increased Risk of Age-Related Macular Degeneration

Thomas M. Hallam et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2020)

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Article Ophthalmology

Complement Activation Levels Are Related to Disease Stage in AMD

Thomas J. Heesterbeek et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2020)

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Review Cell Biology

Complement factor H family proteins in their non-canonical role as modulators of cellular functions

Mihaly Jozsi et al.

SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY (2019)

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Article Biology

Merging organoid and organ-on-a-chip technology to generate complex multi-layer tissue models in a human retina-on-a-chip platform

Kevin Achberger et al.

ELIFE (2019)

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Editorial Material Immunology

Editorial: The Role of Complement in Health and Disease

Maciej Cedzynski et al.

FRONTIERS IN IMMUNOLOGY (2019)

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Article Multidisciplinary Sciences

Single-cell transcriptomics of the human retinal pigment epithelium and choroid in health and macular degeneration

Andrew P. Voigt et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Review Immunology

Regulation of regulators: Role of the complement factor H-related proteins

Marcell Cserhalmi et al.

SEMINARS IN IMMUNOLOGY (2019)

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Article Multidisciplinary Sciences

CFH exerts anti-oxidant effects on retinal pigment epithelial cells independently from protecting against membrane attack complex

Celine Borras et al.

SCIENTIFIC REPORTS (2019)

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Review Immunology

The eye as a complement dysregulation hotspot

Simon J. Clark et al.

SEMINARS IN IMMUNOPATHOLOGY (2018)

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Article Biochemistry & Molecular Biology

Functional analyses of rare genetic variants in complement component C9 identified in patients with age-related macular degeneration

Mariann Kremlitzka et al.

HUMAN MOLECULAR GENETICS (2018)

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Article Ophthalmology

Genome-Wide Association Study Reveals Variants in CFH and CFHR4 Associated with Systemic Complement Activation

Laura Lores-Motta et al.

OPHTHALMOLOGY (2018)

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Article Multidisciplinary Sciences

A monoclonal antibody targeting amyloid β (Aβ) restores complement factor I bioactivity: Potential implications in age-related macular degeneration and Alzheimer's disease

Kameran Lashkari et al.

PLOS ONE (2018)

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Article Medicine, General & Internal

A model to study complement involvement in experimental retinal degeneration

Camilla Mohlin et al.

UPSALA JOURNAL OF MEDICAL SCIENCES (2018)

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Article Multidisciplinary Sciences

Classical and alternative complement activation on photoreceptor outer segments drives monocyte-dependent retinal atrophy

Kenneth J. Katschke et al.

SCIENTIFIC REPORTS (2018)

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Article Multidisciplinary Sciences

C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H: implications for retinal inflammation

Maurice Swinkels et al.

SCIENTIFIC REPORTS (2018)

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Article Immunology

Reference Intervals of Factor H and Factor H-Related Proteins in Healthy Children

Anna E. van Beek et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Article Immunology

Analysis of C3 Gene Variants in Patients With Idiopathic Recurrent Spontaneous Pregnancy Loss

Frida C. Mohlin et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Structural Immunology of Complement Receptors 3 and 4

Thomas Vorup-Jensen et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Article Ophthalmology

A Novel Choroidal Endothelial Cell Line Has a Decreased Affinity for the Age-Related Macular Degeneration-Associated Complement Factor H Variant 402H

Markus A. Loeven et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2018)

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Article Ophthalmology

Local complement activation in aqueous humor in patients with age-related macular degeneration

T. Schick et al.

EYE (2017)

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Article Immunology

Age-related macular degeneration associated polymorphism rs10490924 in ARMS2 results in deficiency of a complement activator

Sven Micklisch et al.

JOURNAL OF NEUROINFLAMMATION (2017)

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Review Biochemistry & Molecular Biology

The complement system in age-related macular degeneration: A review of rare genetic variants and implications for personalized treatment

Maartje J. Geerlings et al.

MOLECULAR IMMUNOLOGY (2017)

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Article Ophthalmology

Prevalence of Age-Related Macular Degeneration in Europe

Johanna M. Colijn et al.

OPHTHALMOLOGY (2017)

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Targeting factor D of the alternative complement pathway reduces geographic atrophy progression secondary to age-related macular degeneration

Brian L. Yaspan et al.

SCIENCE TRANSLATIONAL MEDICINE (2017)

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Article Cell & Tissue Engineering

An Induced Pluripotent Stem Cell Patient Specific Model of Complement Factor H (Y402H) Polymorphism Displays Characteristic Features of Age-Related Macular Degeneration and Indicates a Beneficial Role for UV Light Exposure

Dean Hallam et al.

STEM CELLS (2017)

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The Functional Effect of Rare Variants in Complement Genes on C3b Degradation in Patients With Age-Related Macular Degeneration

Maartje J. Geerlings et al.

JAMA OPHTHALMOLOGY (2017)

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Bruch's Membrane Compartmentalizes Complement Regulation in the Eye with Implications for Therapeutic Design in Age-Related Macular Degeneration

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The Murine Factor H-Related Protein FHR-B Promotes Complement Activation

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Article Biochemistry & Molecular Biology

Altered bioenergetics and enhanced resistance to oxidative stress in human retinal pigment epithelial cells from donors with age-related macular degeneration

Deborah A. Ferrington et al.

REDOX BIOLOGY (2017)

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Article Genetics & Heredity

A large genome-wide association study of age-related macular degeneration highlights contributions of rare and common variants

Lars G. Fritsche et al.

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Article Biochemistry & Molecular Biology

Factor H uptake regulates intracellular C3 activation during apoptosis and decreases the inflammatory potential of nucleosomes

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CELL DEATH AND DIFFERENTIATION (2016)

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Repressed SIRT1/PGC-1α pathway and mitochondrial disintegration in iPSC-derived RPE disease model of age-related macular degeneration

Nady Golestaneh et al.

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Article Multidisciplinary Sciences

A Novel Complotype Combination Associates with Age-Related Macular Degeneration and High Complement Activation Levels in vivo

Constantin C. Paun et al.

SCIENTIFIC REPORTS (2016)

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Article Geriatrics & Gerontology

Higher plasma levels of complement C3a, C4a and C5a increase the risk of subretinal fibrosis in neovascular age-related macular degeneration

Judith Lechner et al.

IMMUNITY & AGEING (2016)

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Article Ophthalmology

Rare Genetic Variants Associated With Development of Age-Related Macular Degeneration

Nicole T. M. Saksens et al.

JAMA OPHTHALMOLOGY (2016)

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Article Immunology

Complement Regular FHR-3 Is Elevated either Locally or Systemically in a Selection of Autoimmune Diseases

Nicole Schaefer et al.

FRONTIERS IN IMMUNOLOGY (2016)

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Review Medicine, General & Internal

Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention

Dimitrios C. Mastellos et al.

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Article Biochemistry & Molecular Biology

Rare genetic variants in the CFI gene are associated with advanced age-related macular degeneration and commonly result in reduced serum factor I levels

David Kavanagh et al.

HUMAN MOLECULAR GENETICS (2015)

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Article Biochemistry & Molecular Biology

Complement Factor H Binds to Human Serum Apolipoprotein E and Mediates Complement Regulation on High Density Lipoprotein Particles

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JOURNAL OF BIOLOGICAL CHEMISTRY (2015)

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Article Ophthalmology

Complement activation and choriocapillaris loss in early AMD: Implications for pathophysiology and therapy

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PROGRESS IN RETINAL AND EYE RESEARCH (2015)

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Off-target Effects in CRISPR/Cas9-mediated Genome Engineering

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MOLECULAR THERAPY-NUCLEIC ACIDS (2015)

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Review Immunology

Complement system part II: role in immunity

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FRONTIERS IN IMMUNOLOGY (2015)

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Review Immunology

Complement system part I - molecular mechanisms of activation and regulation

Nicolas S. Merle et al.

FRONTIERS IN IMMUNOLOGY (2015)

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Article Ophthalmology

Lutein supplementation leads to decreased soluble complement membrane attack complex sC5b-9 plasma levels

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ACTA OPHTHALMOLOGICA (2015)

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Assessment of Proteins Associated With Complement Activation and Inflammation in Maculae of Human Donors Homozygous Risk at Chromosome 1 CFH-to-F13B

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Article Pathology

The Membrane Attack Complex in Aging Human Choriocapillaris Relationship to Macular Degeneration and Choroidal Thinning

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AMERICAN JOURNAL OF PATHOLOGY (2014)

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Review Genetics & Heredity

Age-Related Macular Degeneration: Genetics and Biology Coming Together

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ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS, VOL 15 (2014)

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Article Immunology

Identification of Factor H-like Protein 1 as the Predominant Complement Regulator in Bruch's Membrane: Implications for Age-Related Macular Degeneration

Simon J. Clark et al.

JOURNAL OF IMMUNOLOGY (2014)

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Review Immunology

The Role of Complement in age-Related Macular Degeneration : Heparan Sulphate, a ZIP Code for Complement Factor H?

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JOURNAL OF INNATE IMMUNITY (2014)

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Article Ophthalmology

Systemic Complement Inhibition with Eculizumab for Geographic Atrophy in Age-Related Macular Degeneration

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Functional architecture of the retina: Development and disease

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PROGRESS IN RETINAL AND EYE RESEARCH (2014)

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Article Ophthalmology

Age-Dependent Changes in Heparan Sulfate in Human Bruch's Membrane: Implications for Age-Related Macular Degeneration

Tiarnan D. L. Keenan et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2014)

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Article Biochemistry & Molecular Biology

Functional Anatomy of Complement Factor H

Elisavet Makou et al.

BIOCHEMISTRY (2013)

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Article Biochemistry & Molecular Biology

Genetic influences on plasma CFH and CFHR1 concentrations and their role in susceptibility to age-related macular degeneration

Morad Ansari et al.

HUMAN MOLECULAR GENETICS (2013)

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Article Cell Biology

The complement membrane attack complex triggers intracellular Ca2+ fluxes leading to NLRP3 inflammasome activation

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JOURNAL OF CELL SCIENCE (2013)

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Article Immunology

Tissue-Specific Host Recognition by Complement Factor H Is Mediated by Differential Activities of Its Glycosaminoglycan-Binding Regions

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Article Genetics & Heredity

Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration

Johanna M. Seddon et al.

NATURE GENETICS (2013)

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Article Genetics & Heredity

A functional variant in the CFI gene confers a high risk of age-related macular degeneration

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NATURE GENETICS (2013)

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Article Multidisciplinary Sciences

Association between CFH Y402H Polymorphism and Age Related Macular Degeneration in North Indian Cohort

Neel Kamal Sharma et al.

PLOS ONE (2013)

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Article Multidisciplinary Sciences

The Effect of Lutein Supplementation on Blood Plasma Levels of Complement Factor D, C5a and C3d

Yuan Tian et al.

PLOS ONE (2013)

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Article Ophthalmology

C-Reactive Protein and the Incidence of Macular Degeneration Pooled Analysis of 5 Cohorts

Vinod P. Mitta et al.

JAMA OPHTHALMOLOGY (2013)

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Article Ophthalmology

Altered Expression of CD46 and CD59 on Leukocytes in Neovascular Age-Related Macular Degeneration

Amardeep Singh et al.

AMERICAN JOURNAL OF OPHTHALMOLOGY (2012)

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Article Biochemistry & Molecular Biology

Factor H-related Protein 4 Activates Complement by Serving as a Platform for the Assembly of Alternative Pathway C3 Convertase via Its Interaction with C3b Protein

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Article Ophthalmology

Risk Alleles in CFH and ARMS2 Are Independently Associated with Systemic Complement Activation in Age-related Macular Degeneration

Dzenita Smailhodzic et al.

OPHTHALMOLOGY (2012)

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Article Ophthalmology

C9-R95X Polymorphism in Patients with Neovascular Age-Related Macular Degeneration

Koji M. Nishiguchi et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2012)

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Article Ophthalmology

C-reactive protein and complement factor H in aged human eyes and eyes with age-related macular degeneration

Imran A. Bhutto et al.

BRITISH JOURNAL OF OPHTHALMOLOGY (2011)

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Article Ophthalmology

Elevated membrane attack complex in human choroid with high risk complement factor H genotypes

Robert F. Mullins et al.

EXPERIMENTAL EYE RESEARCH (2011)

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Polyethylene Glycol (PEG)-induced Mouse Model of Choroidal Neovascularization

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JOURNAL OF BIOLOGICAL CHEMISTRY (2011)

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Article Multidisciplinary Sciences

Common polymorphisms in C3, factor B, and factor H collaborate to determine systemic complement activity and disease risk

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2011)

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Article Ophthalmology

Complement Factor D in Age-Related Macular Degeneration

Chloe M. Stanton et al.

INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2011)

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Article Biochemistry & Molecular Biology

Genetic control of the alternative pathway of complement in humans and age-related macular degeneration

Laura A. Hecker et al.

HUMAN MOLECULAR GENETICS (2010)

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Article Biochemistry & Molecular Biology

An imbalance of human complement regulatory proteins CFHR1, CFHR3 and factor H influences risk for age-related macular degeneration (AMD)

Lars G. Fritsche et al.

HUMAN MOLECULAR GENETICS (2010)

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Article Biochemistry & Molecular Biology

Impaired Binding of the Age-related Macular Degeneration-associated Complement Factor H 402H Allotype to Bruch's Membrane in Human Retina

Simon J. Clark et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

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Article Ophthalmology

Progression of Geographic Atrophy and Genotype in Age-Related Macular Degeneration

Michael L. Klein et al.

OPHTHALMOLOGY (2010)

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Article Multidisciplinary Sciences

Structures of C3b in Complex with Factors B and D Give Insight into Complement Convertase Formation

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SCIENCE (2010)

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Article Ophthalmology

Plasma Complement Components and Activation Fragments: Associations with Age-Related Macular Degeneration Genotypes and Phenotypes

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INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE (2009)

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Article Multidisciplinary Sciences

Systemic Complement Activation in Age-Related Macular Degeneration

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PLOS ONE (2008)

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Article Ophthalmology

Estimation of systemic complement C3 activity in age-related macular degeneration

Sobha Sivaprasad et al.

ARCHIVES OF OPHTHALMOLOGY (2007)

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Article Multidisciplinary Sciences

Individuals homozygous for the age-related macular degeneration risk-conferring variant of complement factor H have elevated levels of CRP in the choroid

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2006)

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Article Genetics & Heredity

Two factor H-related proteins from the mouse:: expression analysis and functional characterization

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IMMUNOGENETICS (2006)

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Article Genetics & Heredity

A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration

Anne E. Hughes et al.

NATURE GENETICS (2006)

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Article Biochemistry & Molecular Biology

His-384 allotypic variant of factor H associated with age-related macular degeneration has different heparin binding properties from the non-disease-associated form.

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JOURNAL OF BIOLOGICAL CHEMISTRY (2006)

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Review Biochemistry & Molecular Biology

Matrix metalloproteinase-8: Cleavage can be decisive

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CYTOKINE & GROWTH FACTOR REVIEWS (2006)

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Extended haplotypes in the complement factor H (CFH) and CFH-related (CFHR) family of genes protect against age-related macular degeneration: Characterization, ethnic distribution and evolutionary implications

Gregory S. Hageman et al.

ANNALS OF MEDICINE (2006)

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Article Multidisciplinary Sciences

A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration

GS Hageman et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

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Article Multidisciplinary Sciences

Complement factor H polymorphism in age-related macular degeneration

RJ Klein et al.

SCIENCE (2005)

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Article Multidisciplinary Sciences

Complement factor H polymorphism and age-related macular degeneration

AO Edwards et al.

SCIENCE (2005)

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Article Multidisciplinary Sciences

Complement factor H variant increases the risk of age-related macular degeneration

JL Haines et al.

SCIENCE (2005)

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Review Biochemistry & Molecular Biology

Drusen associated with aging and age-related macular degeneration contain proteins common to extracellular deposits associated with atherosclerosis, elastosis, amyloidosis, and dense deposit disease

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