Pluripotent stem cell-derived models of retinal disease: Elucidating pathogenesis, evaluating novel treatments, and estimating toxicity

Progress in Retinal and Eye Research, Journal Year: 2024, Volume and Issue: 100, P. 101248 - 101248

Published: Feb. 16, 2024

Blindness poses a growing global challenge, with approximately 26% of cases attributed to degenerative retinal diseases. While gene therapy, optogenetic tools, photosensitive switches, and prostheses offer hope for vision restoration, these high-cost therapies will benefit few patients. Understanding diseases is therefore key advance effective treatments, requiring in vitro models replicating pathology allowing quantitative assessments drug discovery. Pluripotent stem cells (PSCs) provide unique solution given their limitless supply ability differentiate into light-responsive tissues encompassing all cell types. This review focuses on the history current state photoreceptor pigment epithelium (RPE) generation from PSCs. We explore applications this technology disease modelling, experimental therapy testing, biomarker identification, toxicity studies. consider challenges scalability, standardisation, reproducibility, stress importance incorporating vasculature immune organoids. advocate high-throughput automation data acquisition analyses underscore value advanced micro-physiological systems that fully capture interactions between neural retina, RPE, choriocapillaris.

Language: Английский

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REACH out-numbered! The future of REACH and animal numbers

ALTEX, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 1, 2023

Policy impact analysis is needed for evidence-based policy-making.Numbers are not always fun. "Statistics the triumph of quantitative method, and method victory sterility death" a quote from Franco-English writer Hilaire Belloc (1870Belloc ( -1953)).Bad policies even less fun.There tremendous difference between statistics predictions.With more data becoming available, we can fine-tune predictions, but this requires us to look at where forecasts were off. IntroductionWe have once again (Knight et al., 2023) attempted bring animal numbers into policy discussion around Europe's Chemicals Regulation REACH.The American science fiction

Language: Английский

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Alternative methods go green! Green toxicology as a sustainable approach for assessing chemical safety and designing safer chemicals

ALTEX, Journal Year: 2024, Volume and Issue: 41(1)

Published: Jan. 1, 2024

Green toxicology is marching chemistry into the 21st century. This emerging framework will transform how chemical safety evaluated by incorporating evaluation of hazards, exposures, and risks associated with chemicals early product development in a way that minimizes adverse impacts on human environmental health. The goal to minimize toxic threats across entire supply chains through smarter designs policies. Traditional animal testing methods are replaced faster, cutting-edge innovations like organs-on-chips artificial intelligence predictive models also more cost-effective. Core principles green include utilizing alternative test methods, applying precautionary principle, considering lifetime impacts, emphasizing risk prevention over reaction. paper provides an overview these foundational concepts describes current initiatives future opportunities advance adoption approaches. Chal­lenges limitations discussed. shoots governments offering carrots European Deal nudge industry. Noteworthy, rights environ­mental groups have different ideas about needs for their consequences use. represents forward support both societal sufficient throughput relevance hazard information minimal suffering. toxi­cology thus sets stage synergize health ecological values. Overall, integration has potential profoundly shift managed achieve goals ethical, ecologically-conscious manner. Plain language summary aims make safer design. It focuses preventing toxicity issues during instead after products developed. uses modern non-animal computer lab tests cells predict if chem­icals could be hazardous. Benefits faster results, lower costs, less testing. using tests, caution even uncertain data, con­sidering global chains, article highlights US policy efforts spur sustainable innovation which necessitate greener approaches assess new materials drive adoption. seeks integrate design so valued equally functionality profit. alignment promises safer, ethical but faces chal­lenges around validating overcoming institutional resistance change.

Language: Английский

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Revolutionizing developmental neurotoxicity testing – a journey from animal models to advanced in vitro systems

ALTEX, Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

Developmental neurotoxicity (DNT) testing has seen enormous progress over the last two decades. Preceding even publication of animal-based OECD test guideline for DNT in 2007, a series non-animal technology workshops and conferences (starting 2005) shaped community that delivered comprehensive battery vitro methods (IVB). Its data interpretation is covered by very recent guidance (No. 377). Here, we aim to overview field, focusing on evolution strategies, role emerging technologies, impact guidelines testing. In particular, this an example targeted development animal-free approach one most complex hazards chemicals human health. These developments started literally from blank slate, with no proposed alternative available. Over decades, cutting-edge science enabled design spares animals enables throughput challenging hazard. While it evident field needs regulation, massive economic decreased cognitive capacity caused chemical exposure should be prioritized more highly. Beyond this, claim fame scientific brought understanding brain, its development, how can perturbed. Plain language summaryDevelopmental predicts hazard brain development. Comprehensive advanced strategies using now replace approaches assess large numbers accurately efficiently than approach. Recent formalized DNT, marking pivotal achievement field. The shift towards reflects both commitment animal welfare growing recognition public health impacts associated impaired function exposures. innovations ultimately contribute safer management better protection health, especially during vulnerable stages

Language: Английский

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Investigating the applicability domain of the hiPSC-based PluriLum assay: an embryotoxicity assessment of chemicals and drugs

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(4), P. 1209 - 1224

Published: Feb. 4, 2024

Abstract To meet the growing demand for developmental toxicity assessment of chemicals, New Approach Methodologies (NAMs) are needed. Previously, we developed two 3D in vitro assays based on human-induced pluripotent stem cells (hiPSC) and cardiomyocyte differentiation: PluriBeat assay, beating differentiated embryoid bodies, PluriLum a reporter gene assay expression early cardiac marker NKX2.5 ; both promising predicting embryotoxic effects chemicals drugs. In this work, aimed to further describe predictive power compare its sensitivity with similar human cell-based by others. For purpose, assessed panel ten from different chemical classes, consisting known toxicants 5-fluorouracil, all- trans retinoic acid valproic acid, as well negative control compounds ascorbic folic acid. addition, fungicides epoxiconazole prochloraz, three perfluoroalkyl substances (PFAS), PFOS, PFOA GenX were tested. Generally, displayed higher when compared assay. several luminescence readout showed not detected including PFAS fungicides. Overall, find that has potential provide fast objective detection level is comparable or than other also differentiation toxicity.

Language: Английский

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Green Toxicology

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

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Read-across-driven binary classification for the developmental and reproductive toxicity of organic compounds tested according to the OECD test guidelines 421/422

SAR and QSAR in environmental research, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 24

Published: April 17, 2025

Developmental and reproductive toxicity (DART) refers to the adverse effects on sexual function, fertility, development of offspring resulting from exposure toxic substances or chemicals, which may occur at various stages cycle. In response increasing volume regulatory bodies advocate for implementing new approach methodologies (NAMs) as alternatives animal testing, enabling rapid assessments potential numerous chemical substances. this study, in silico were utilized assess DART properties industrial chemicals. We employed a Read-Across (RA)-based binary classification evaluate these The data have been compiled two distinct sources: eChemPortal (https://www.echemportal.org/echemportal/) National Institute Health Sciences (NIHS) databases. information gathered sources encompasses types data: No Observed Adverse Effect Level (NOAEL) Low (LOAEL) tested per Organisation Economic Co-operation Development Test Guidelines 421 422, adopting principles Good Laboratory Practice (GLP). separately safety assessment through classification-based read-across prediction, demonstrating commendable capabilities chemicals (Accuracytest ~0.700).

Language: Английский

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Revealing an adverse outcome pathway network for reproductive toxicity induced by atrazine, via oxidative stress

Computational Toxicology, Journal Year: 2024, Volume and Issue: 30, P. 100317 - 100317

Published: May 20, 2024

Language: Английский

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A developmental and reproductive toxicity adverse outcome pathway network to support safety assessments

Computational Toxicology, Journal Year: 2024, Volume and Issue: 31, P. 100325 - 100325

Published: Aug. 8, 2024

Language: Английский

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New Approach Methodologies (NAMs) to Support Regulatory Decisions for Chemical Safety

FSA research and evidence., Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

Language: Английский

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