Review
Biochemistry & Molecular Biology
Young Gun Park, Yong Soo Park, In-Beom Kim
Summary: Age-related macular degeneration (AMD) is a complex disease characterized by neovascularization or geographic atrophy. The complement system plays a crucial role in AMD and has become a therapeutic target. Further research is needed to fully understand the mechanism of complement disease propagation in AMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Angela Armento, Marius Ueffing, Simon J. Clark
Summary: Age-related macular degeneration (AMD) is a complex disease with genetic, aging, and lifestyle factors all playing a role in its onset and progression. Therapeutic attempts targeting the complement system have not been successful, highlighting the complexity of AMD beyond genetic factors.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Ophthalmology
Lebriz Altay, Julia Lemke, Jutta Schroeder-Braunstein, Caroline Gietzelt, Vasilena Sitnilska, Friederike Schaub, Claus Cursiefen, Philip Enders, Sascha Fauser
Summary: The aim of this study was to investigate the influence of dietary supplementation using Age-Related Eye Disease Study 2 (AREDS2) on complement activation in patients with neovascular age-related macular degeneration (nAMD) under ongoing treatment. The results showed that short-term dietary AREDS2 supplementation leads to a significant increase in systemic zinc levels without any influence on complement activation levels.
Review
Biochemistry & Molecular Biology
Niloofar Piri, Henry J. Kaplan
Summary: AMD is a progressive degenerative disease that severely affects central vision in people over age 50, impacting their ability to read, write, drive, and recognize faces. The disease is complex and multifactorial, involving age, genetics, and environmental factors. The role of complement system in the development of AMD is reviewed. Understanding the pathophysiology of AMD and its risk factors is crucial for drug discovery.
Review
Ophthalmology
Shenouda Girgis, Lawrence R. Lee
Summary: Age-related macular degeneration is a global disease with a significant social impact, and the treatment of neovascular AMD has been revolutionized by the advent of anti-VEGF therapy. Currently, investigations are being conducted for possible therapeutic options for dry AMD. Various treatments, including complement pathway inhibitors, visual cycle modulators, antioxidative therapy, gene therapy, and stem cell therapy, are undergoing clinical trials. Two intravitreal anti-complement factors have shown promising results in reducing the growth of geographic atrophy.
CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY
(2023)
Article
Medicine, General & Internal
Jonathan B. Lin, Stylianos Serghiou, Joan W. Miller, Demetrios G. Vavvas
Summary: Complement dysregulation is observed in early/intermediate nonexudative AMD, but not in patients with geographic atrophy. These findings provide insights into the mechanism of AMD and inform future clinical trials.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Ophthalmology
John T. Demirs, Junzheng Yang, Maura A. Crowley, Michael Twarog, Omar Delgado, Yubin Qiu, Stephen Poor, Dennis S. Rice, Thaddeus P. Dryja, Karen Anderson, Sha-Mei Liao
Summary: The dysregulation of the alternative complement pathway is a major pathogenic mechanism in age-related macular degeneration. Complement mRNA and protein expression levels were found to be significantly higher in macular retinal pigment epithelium/choroid tissue than in the neural retina, regardless of AMD grade status. The study suggests that the RPE/choroid is the primary site for complement inhibition to treat geographic atrophy or earlier stages of the disease.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2021)
Review
Biochemistry & Molecular Biology
Prem N. Patel, Parth A. Patel, Matthew R. Land, Ibrahim Bakerkhatib-Taha, Harris Ahmed, Veeral Sheth
Summary: Age-related macular degeneration (AMD) is a common cause of vision loss in elderly individuals. The pathophysiology of dry AMD is associated with key proteins in the complement cascade, providing potential therapeutic targets. Early intervention may prevent disease progression.
Review
Pharmacology & Pharmacy
Matteo Stravalaci, Mariantonia Ferrara, Varun Pathak, Francesca Davi, Barbara Bottazzi, Alberto Mantovani, Reinhold J. Medina, Mario R. Romano, Antonio Inforzato
Summary: Age related macular degeneration (AMD) and diabetic retinopathy (DR) are neurodegenerative and inflammatory diseases of the eye. Both diseases involve cellular components of the blood-retina barrier (BRB) and share common drivers, such as chronic inflammation. Long pentraxin 3 (PTX3), a soluble pattern recognition molecule, is emerging as a potential therapeutic target in retinal diseases, as it plays a role in trapping complement and modulating inflammation at the BRB.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Immunology
Yingbo Ma, Xueqing Ding, Mingxi Shao, Yichao Qiu, Shengjie Li, Wenjun Cao, Gezhi Xu
Summary: This study investigated the association between serum complement components and AMD. The results showed that higher levels of C1q and lower levels of C3 were associated with increased risk of AMD in female patients. This suggests that the complement classical pathway may be involved in the development of AMD, especially in females.
JOURNAL OF INFLAMMATION RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Chloe N. Thomas, Dawn A. Sim, Wen Hwa Lee, Nada Alfahad, Andrew D. Dick, Alastair K. Denniston, Lisa J. Hill
Summary: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world, with the need for new therapies to address disease progression and treatment challenges at different stages.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Review
Immunology
Sarah de Jong, Jiaqi Tang, Simon J. Clark
Summary: Age-related macular degeneration (AMD) is a major cause of vision impairment, but currently there is no effective treatment for the majority of patients. Studies have shown that the complement system and remodeling of the extracellular matrix play a significant role in AMD. Excessive activation of the complement system can lead to tissue damage and complement-associated diseases like AMD. The latest findings suggest abnormal activation of the alternative pathway in AMD patients, which has important implications for future clinical trials and treatment prospects.
IMMUNOLOGICAL REVIEWS
(2023)
Review
Medicine, General & Internal
Phoebe Lin, Scott M. McClintic, Urooba Nadeem, Dimitra Skondra
Summary: The intestinal microbiota plays a crucial role in AMD pathogenesis, with growing evidence suggesting that environmental factors associated with AMD progression potentially work through the intestinal microbiota. There is a correlation between intestinal dysbiosis and AMD pathogenesis, while AREDS supplementation can reverse adverse intestinal microbial changes.
JOURNAL OF CLINICAL MEDICINE
(2021)
Review
Medicine, General & Internal
Sarah Hammadi, Nikolaos Tzoumas, Mariantonia Ferrara, Ingrid Porpino Meschede, Katharina Lo, Claire Harris, Majlinda Lako, David H. Steel
Summary: The complement system is essential for the body's defense against pathogens, but dysregulation can lead to diseases such as age-related macular degeneration (AMD). Complement activation occurs in various parts of the eye, including the choriocapillaris and the subretinal and retinal pigment epithelium spaces. The barrier of Bruch's membrane impedes complement protein diffusion and its dysfunction contributes to AMD pathogenesis. This review examines the structure of Bruch's membrane, its age-related changes, and the potential of different delivery routes for complement inhibitors in treating AMD.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Oncology
Andrea P. Cabrera, Jonathan Stoddard, Irene Santiago Tierno, Nikolaos Matisioudis, Mahesh Agarwal, Lauren Renner, Neha Palegar, Martha Neuringer, Trevor McGill, Kaustabh Ghosh
Summary: The study found differences in the characteristics of choroidal endothelial cells in young and old monkey eyes, with cells in older eyes being stiffer and more susceptible to complement activation-induced damage. These differences may be related to the activities of the mechanical structure regulators Rac and Rho in the cells. These findings offer new mechanistic insights into choroidal vascular loss in early AMD and warrant further investigation for translational potential.
JOURNAL OF PATHOLOGY
(2022)
Article
Medicine, Research & Experimental
Hugo G. B. Nijmeijer, Hans M. M. Groenewoud, Emmanuel A. M. Mylanus, Andre Goedegebure, Wendy J. Huinck, Gert Jan van der Wilt
Summary: This study aimed to explore the impact of further expanding unilateral cochlear implant (CI) criteria in individuals with severe hearing loss (HL) on the number of CI recipients, costs, quality of life, and cost-effectiveness. The results indicated that expanding eligibility to persons with severe HL could be a cost-effective use of resources, but it would require an increase in diagnostic, operative, and rehabilitative capacity.
Article
Geriatrics & Gerontology
Laura Kananen, Mikko Hurme, Alexander Buerkle, Maria Moreno-Villanueva, Jurgen Bernhardt, Florence Debacq-Chainiaux, Beatrix Grubeck-Loebenstein, Marco Malavolta, Andrea Basso, Francesco Piacenza, Sebastiano Collino, Efstathios S. Gonos, Ewa Sikora, Daniela Gradinaru, Eugene H. J. M. Jansen, Martijn E. T. Dolle, Michel Salmon, Wolfgang Stuetz, Daniela Weber, Tilman Grune, Nicolle Breusing, Andreas Simm, Miriam Capri, Claudio Franceschi, Eline Slagboom, Duncan Talbot, Claude Libert, Jani Raitanen, Seppo Koskinen, Tommi Harkanen, Sari Stenholm, Mika Ala-Korpela, Terho Lehtimaki, Olli T. Raitakari, Olavi Ukkola, Mika Kahonen, Marja Jylha, Juulia Jylhava
Summary: Circulating cell-free DNA (cf-DNA) levels are associated with age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes, and various biomarkers. Higher cf-DNA levels were found in men, especially middle-aged men and women who smoke, and older frail individuals. Inflammatory markers, metabolites, and antioxidant levels were correlated with cf-DNA levels. These findings have implications for future studies on the epidemiology and biological mechanisms of cf-DNA and its potential as a clinical marker.
Article
Endocrinology & Metabolism
Mika Ala-Korpela, Terho Lehtimaki, Mika Kahonen, Jorma Viikari, Markus Perola, Veikko Salomaa, Johannes Kettunen, Olli T. Raitakari, Ville-Petteri Makinen
Summary: This study tested whether cross-sectional modeling can distinguish slow vs accelerated aging in a human population. A machine learning model was trained to predict age and tested against longitudinal data. The results showed that the cross-sectional proxy failed to predict longitudinal observations, suggesting that differences in starting points may explain diverging aging rates.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Computer Science, Interdisciplinary Applications
Shuhe Zhang, Tao Peng, Zeyu Ke, Han Yang, Tos T. J. M. Berendschot, Jinhua Zhou
Summary: In this study, the Retinex-qDPC method is proposed to improve the quality of phase recovery in the presence of mismatched background. By utilizing the edge features of images, the Retinex-qDPC models achieve high background-robustness qDPC reconstruction. The L1-Retinex-qDPC outperforms other state-of-the-art qDPC algorithms.
COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE
(2023)
Article
Neurosciences
Frank C. T. van der Heide, Sara Mokhtar, Anjani Khanna, Mozhda Said, Ronald M. A. Henry, Abraham A. Kroon, Pieter C. Dagnelie, Simone J. P. M. Eussen, Tos T. J. M. Berendschot, Jan S. A. G. Schouten, Miranda T. Schram, Carla J. H. van der Kallen, Marleen M. J. van Greevenbroek, Anke Wesselius, Hans H. C. M. Savelberg, Nicolaas C. Schaper, Carroll A. B. Webers, Coen D. A. Stehouwer
Summary: This study found significant associations between dementia risk factors (such as hyperglycemia, unhealthy diet, lower cardiorespiratory fitness, smoking, alcohol consumption, and hypertension) and lower retinal sensitivity and retinal nerve fiber layer thickness. These findings suggest that retinal neural indices may serve as biomarkers for monitoring therapeutic strategies aimed at preventing early-stage cerebral neurodegeneration and dementia.
JOURNAL OF ALZHEIMERS DISEASE
(2023)
Letter
Ophthalmology
Magali M. S. Vandevenne, Valentijn S. C. Webers, Maartje H. M. Segers, Tos T. J. M. Berendschot, David Zadok, Mor M. Dickman, Rudy M. M. A. Nuijts, Adi Abulafia
JOURNAL OF CATARACT AND REFRACTIVE SURGERY
(2023)
Article
Multidisciplinary Sciences
Havard Aanes, Oyvind Bleka, Pal Skage Dahlberg, Kristina Totland Carm, Terho Lehtimaki, Olli Raitakari, Mika Kahonen, Mikko Hurme, Veslemoy Rolseth
Summary: More than 1/4 of children globally lack documentation of their date of birth, emphasizing the need for biological methods to predict age. DNA methylation is the most promising biomarker for age assessment, but there is currently no epigenetic clock specifically designed for adolescents and young adults. A novel age predictor called PAYA, using 267 CpG methylation sites, shows potential for age assessment in this population, but further research is needed to test its robustness across different populations and environments.
SCIENTIFIC REPORTS
(2023)
Article
Multidisciplinary Sciences
Miikael Lehtimaki, Binisha H. H. Mishra, Coral Del-Val, Leo-Pekka Lyytikainen, Mika Kahonen, C. Robert Cloninger, Olli T. T. Raitakari, Reijo Laaksonen, Igor Zwir, Terho Lehtimaki, Pashupati P. P. Mishra
Summary: This study used an unsupervised machine learning method called PGMRA to discover the genotype-lipidome relations in a Finnish population. The researchers found 93 statistically significant lipidome-genotype relations, which contained a total of 5977 SNPs across 3164 genes. Twenty nine of these relations represented distinct subgroups with unique SNPs and participants. Pathway enrichment analysis identified 30 significantly enriched biological processes related to plasma lipid metabolism. These findings have implications for precision medicine research.
SCIENTIFIC REPORTS
(2023)
Article
Cardiac & Cardiovascular Systems
Juhani S. Koskinen, Ville Kyto, Markus Juonala, Jorma S. A. Viikari, Jaakko Nevalainen, Mika Kahonen, Terho Lehtimaki, Nina Hutri-Kahonen, Tomi P. Laitinen, Paivi Tossavainen, Eero Jokinen, Costan G. Magnussen, Olli T. Raitakari
Summary: This study examines the association between childhood and adult dyslipidemia and adult carotid atherosclerotic plaques, and found that childhood dyslipidemia, even if resolved by adulthood, is still a risk factor for adult carotid plaques.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Neurosciences
Simo-Pekko Salminen, Anssi Solismaa, Leo-Pekka Lyytikainen, Vesa Paavonen, Nina Mononen, Terho Lehtimaki, Esa Leinonen, Olli Kampman
Summary: This study examined the clustering of Cloninger's temperament dimensions and their association with single nucleotide polymorphisms (SNPs). The results showed that multiple SNPs from different genes were associated with different temperament clusters. Genetic risk scores (GRSs) were also found to be associated with individuals' temperament profiles. However, further research is needed to explore the clinical applicability of these clusters.
ACTA NEUROPSYCHIATRICA
(2023)
Article
Ophthalmology
Antoni Vallbona-Garcia, Ilse H. J. Hamers, Florence H. J. van Tienen, Juan Ochoteco-Asensio, Tos T. J. M. Berendschot, Irenaeus F. M. de Coo, Birke J. Benedikter, Carroll A. B. Webers, Hubert J. M. Smeets, Theo G. M. F. Gorgels
Summary: This study found that primary open-angle glaucoma (POAG) is characterized by optic nerve degeneration and irreversible loss of retinal ganglion cells. The results showed that POAG patients with high intraocular pressure (HTG) have a lower number of mitochondrial DNA copies, potentially indicating a deficient mitochondrial replication.
EXPERIMENTAL EYE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Yordi van de Vegte, Ruben P. Eppinga, M. Yldau van der Ende, Yanick Hagemeijer, Yuvaraj V. Mahendran, Elias Y. Salfati, Albert E. Smith, Vanessa Tan, Dan V. Arking, Ioanna Ntalla, Emil A. Appel, Claudia Schurmann, Jennifer Brody, Rico Rueedi, Ozren Polasek, Gardar Sveinbjornsson, Cecile Lecoeur, Claes Ladenvall, Jing Hua Zhao, Aaron Isaacs, Lihua Wang, Jian'an Luan, Shih-Jen Hwang, Nina U. Mononen, Kirsi F. Auro, Anne Jackson, Lawrence Bielak, Linyao Zeng, Nabi Shah, Maria Nethander, Archie Campbell, Tuomo Rankinen, Sonali Pechlivanis, Lu Qi, Wei Zhao, Federica Rizzi, Toshiko Tanaka, Antonietta Robino, Massimiliano Cocca, Leslie Lange, Martina Mueller-Nurasyid, Carolina E. Roselli, Weihua Zhang, Marcus J. Kleber, Xiuqing Guo, Henry E. Lin, Francesca Pavani, Tessel Galesloot, Raymond E. Noordam, Yuri Milaneschi, Katharina Schraut, Marcel den Hoed, Frauke E. Degenhardt, Stella Trompet, Marten van den Berg, Giorgio Pistis, Yih-Chung S. Tham, Stefan L. Weiss, Xueling J. Sim, Hengtong M. Li, Peter van der Most, Ilja Nolte, Leo-Pekka R. Lyytikaeinen, M. Abdullah Said, Daniel Witte, Carlos M. Iribarren, Lenore S. Launer, Susan Ring, Paul de Vries, Peter P. Sever, Allan Linneberg, Erwin M. Bottinger, Sandosh Padmanabhan, Bruce Psaty, Nona Sotoodehnia, Ivana Kolcic, Delnaz D. Roshandel, Andrew O. Paterson, David F. Arnar, Daniel Gudbjartsson, Hilma Holm, Beverley T. Balkau, Claudia H. Silva, Christopher Newton-Cheh, Kjell Nikus, Perttu L. Salo, Karen A. Mohlke, Patricia Peyser, Heribert Schunkert, Mattias Lorentzon, Jari C. Lahti, Dabeeru C. Rao, Marilyn D. Cornelis, Jessica A. Faul, Jennifer Smith, Katarzyna Stolarz-Skrzypek, Stefania Bandinelli, Maria Pina Concas, Gianfranco Sinagra, Thomas Meitinger, Melanie F. Waldenberger, Moritz Sinner, Konstantin E. Strauch, Graciela D. Delgado, Kent Taylor, Jie Yao, Luisa Foco, Olle Melander, Jacqueline de Graaf, Renee de Mutsert, Eco J. C. de Geus, Asa K. Johansson, Peter K. Joshi, Lars Lind, Andre W. Franke, Peter V. Macfarlane, Kirill Tarasov, Nicholas B. Tan, Stephan Felix, E-Shyong Q. Tai, Debra Quek, Harold Snieder, Johan Ormel, Martin Ingelsson, Cecilia P. Lindgren, Andrew T. Morris, Olli Raitakari, Torben Hansen, Themistocles Assimes, Vilmundur J. Gudnason, Nicholas C. Timpson, Alanna B. Morrison, Patricia P. Munroe, David Strachan, Niels Grarup, Ruth J. F. R. Loos, Susan Heckbert, Peter Vollenweider, Caroline Hayward, Kari Stefansson, Philippe Froguel, Leif J. Groop, Nicholas M. Wareham, Cornelia F. van Duijn, Mary J. Feitosa, Christopher O'Donnell, Mika Kaehoenen, Markus Perola, Michael Boehnke, Sharon L. R. Kardia, Jeanette Erdmann, Colin N. A. Palmer, Claes J. Ohlsson, David G. Porteous, Johan Eriksson, Claude Bouchard, Susanne Moebus, Peter R. Kraft, David Weir, Daniele Cusi, Luigi Ferrucci, Sheila Ulivi, Giorgia Girotto, Adolfo Correa, Stefan Kaeaeb, Annette C. Peters, John S. Chambers, Jaspal Kooner, Winfried I. Maerz, Jerome A. Rotter, Andrew Hicks, J. Gustav Smith, Lambertus A. L. M. O. Kiemeney, Dennis Mook-Kanamori, Brenda W. J. H. Penninx, Ulf F. Gyllensten, James Wilson, Stephen Burgess, Johan Sundstroem, Wolfgang Lieb, J. Wouter Jukema, Mark Eijgelsheim, Edward L. M. Lakatta, Ching-Yu Cheng, Marcus Doerr, Tien-Yin Wong, Charumathi J. Sabanayagam, Albertine Oldehinkel, Harriette Riese, Terho Lehtimaeki, Niek Verweij, Pim van der Harst
Summary: This study identifies new genetic variants associated with resting heart rate (RHR) and demonstrates that higher genetically predicted RHR is associated with a decreased risk of atrial fibrillation and ischemic stroke. Genome-wide analysis reveals multiple genetic variants in cardiomyocyte-related genes and provides insights into their electrocardiogram (ECG) signature. Mendelian randomization analyses indicate that higher genetically predicted RHR increases the risk of dilated cardiomyopathy, but reduces the risk of atrial fibrillation, ischemic stroke, and cardio-embolic stroke.
NATURE COMMUNICATIONS
(2023)
Meeting Abstract
Ophthalmology
M. H. M. Segers, A. Abulafia, V. S. C. Webers, J. -W. Verstraaten, M. M. S. Vandevenne, T. T. J. M. Berendschot, G. D. Barrett, R. M. M. A. Nuijts, M. M. Dickman
ACTA OPHTHALMOLOGICA
(2023)
Proceedings Paper
Computer Science, Artificial Intelligence
Nicholas Matsumoto, Anil Kumar Saini, Pedro Ribeiro, Hyunjun Choi, Alena Orlenko, Leo-Pekka Lyytikainen, Jari O. Laurikka, Terho Lehtimaki, Sandra Batista, Jason H. Moore
Summary: In this paper, we compare the role of two commonly used parent selection methods in evolving machine learning pipelines in TPOT. Results show that lexicase selection leads to significantly faster convergence compared to NSGA-II. We also compare the exploration of the search space by these selection methods using a trie data structure.
GENETIC PROGRAMMING, EUROGP 2023
(2023)
Article
Biotechnology & Applied Microbiology
Pashupati P. Mishra, Binisha H. Mishra, Emma Raitoharju, Nina Mononen, Jorma Viikari, Markus Juonala, Nina Hutri-Kahonen, Mika Kahonen, Olli T. Raitakari, Terho Lehtimaki
Summary: Advanced integrative analysis of DNA methylation and transcriptomics data reveals the effects of smoke-induced epigenetic alterations on gene expression and biological processes, linking smoking and related diseases.
OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY
(2023)
