Functional investigation suggests CNTNAP5 involvement in glaucomatous neurodegeneration obtained from a GWAS in primary angle closure glaucoma DOI Creative Commons
Sudipta Chakraborty,

Jyotishman Sarma,

Shantanu Saha Roy

et al.

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(12), P. e1011502 - e1011502

Published: Dec. 5, 2024

Primary angle closure glaucoma (PACG) affects more than 20 million people worldwide, with an increased prevalence in south-east Asia. In a prior haplotype-based Genome Wide Association Study (GWAS), we identified novel CNTNAP5 genic region, significantly associated PACG. the current study, have extended our perception of involvement glaucomatous neurodegeneration zebrafish model, through investigating phenotypic consequences pertinent to retinal degeneration upon knockdown cntnap5 by translation-blocking morpholinos. While was successfully validated using antibody, immunofluorescence followed western blot analyses cntnap5-morphant (MO) revealed expression acetylated tubulin indicative perturbed cytoarchitecture layers. Moreover, significant loss Nissl substance is observed neuro-retinal layers cntnap5-MO eye, indicating neurodegeneration. Additionally, spontaneous movement behavioural analysis, lower average distance traversed light phase compared mismatch-controls, whereas no difference dark phase, corroborating vision zebrafish. This study provides first direct functional evidence putative role visual

Language: Английский

DNA Methyltransferase Expression (DNMT1, DNMT3a, and DNMT3b) as a Potential Biomarker in Age-Related Macular Degeneration DOI Open Access
Pedro Camacho, Edna Ribeiro, Bruno Pereira

et al.

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 559 - 559

Published: Jan. 16, 2025

Background/Objectives: Age-related macular degeneration (AMD) is a global cause of vision loss, with limited therapeutic options highlighting the need for effective biomarkers. This study aimed to characterize plasma DNA methyltransferase expression (DNMT1, DNMT3A, and DNMT3B) in AMD patients explore divergent patterns across different stages AMD. Methods: Thirty-eight were prospectively enrolled stratified by disease severity: eAMD, iAMD, nAMD, aAMD. Comprehensive ophthalmological assessments performed, including best-corrected visual acuity, digital color fundus photographs, Spectral Domain Optical Coherence Tomography. Peripheral blood samples collected RNA extraction qRT-PCR access epigenetic effectors’ transcriptional expression, namely DNMT1, DNMT3B genes. The data analyzed using IBM SPSS 29. Results: DNMT1 was significantly downregulated late (−0.186 ± 0.341) compared early/intermediate (0.026 0.246). Within AMD, aAMD exhibited marked downregulation (−0.375 0.047) nAMD (0.129 0.392). DNMT3A showed similar patterns, correlating stage. Conclusions: identified stage-specific differences DNMT emphasizing its potential as biomarker progression target future research into personalized strategies.

Language: Английский

Citations

1
Glutathione and a Pool of Metabolites Partly Related to Oxidative Stress Are Associated with Low and High Myopia in an Altered Bioenergetic Environment DOI Creative Commons

Salvador Mérida,

Amparo Návea, Carmen Desco

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(5), P. 539 - 539

Published: April 27, 2024

Oxidative stress forms part of the molecular basis contributing to development and manifestation myopia, a refractive error with associated pathology that is increasingly prevalent worldwide subsequently leads an upsurge in degenerative visual impairment due conditions are especially high myopia. The purpose our study was examine interrelation potential oxidative-stress-related metabolites found aqueous humor high-myopic, low-myopic, non-myopic patients within clinical study. We conducted cross-sectional study, selecting two sets undergoing cataract surgery. first set, which used analyze through NMR assay, comprised 116 patients. A total 59 were assigned quantified. PLS-DA score plot clearly showed separation minimal overlap between HM control samples. model allowed us determine 31 major metabolite differences groups. Complementary statistical analysis data six presented significant among experimental groups (p < 005). number these discovered have direct or indirect connection oxidative linked myopic eyes. Notably, we identified bioenergetic pathways undergone methylation, along choline its derivatives. second set consisted 73 who underwent glutathione assay. Here, variations both reduced oxidized all patient 0.01) for time. Axial length, status, complete ophthalmologic examination also recorded, interrelations metabolic parameters evaluated.

Language: Английский

Citations

5
Epigenome–metabolism nexus in the retina: implications for aging and disease DOI Creative Commons
Anupam K. Mondal, Mohita Gaur, Jayshree Advani

et al.

Trends in Genetics, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Intimate links between epigenome modifications and metabolites allude to a crucial role of cellular metabolism in transcriptional regulation. Retina, being highly metabolic tissue, adapts by integrating inputs from genetic, epigenetic, extracellular signals. Precise global epigenomic signatures guide development homeostasis the intricate retinal structure function. Epigenomic realignment are hallmarks aging highlight link epigenome–metabolism nexus with aging-associated multifactorial traits affecting retina, including age-related macular degeneration glaucoma. Here, we focus on emerging principles control gene regulation, emphasis their contribution human disease. In addition, discuss potential mitigation strategies involving lifestyle changes that target epigenome-metabolome relationship for maintaining

Language: Английский

Citations

4
RNA Methylation Homeostasis in Ocular Diseases: All Eyes on Me DOI
Jieling Tang, Chuandi Zhou, Fuxiang Ye

et al.

Progress in Retinal and Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 101335 - 101335

Published: Jan. 1, 2025

Language: Английский

Citations

0
AnimalGWASAtlas: annotation and prioritization of GWAS loci and quantitative trait loci for animal complex traits DOI Creative Commons

Yuwei Gou,

Yunhan Jing,

Yifei Wang

et al.

Journal of Biological Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108267 - 108267

Published: Feb. 1, 2025

Genome-wide association study (GWAS) and quantitative trait locus (QTL) mapping methods provide valuable insights opportunities for identifying functional gene underlying phenotype formation. However, the majority of GWAS risk loci QTLs located in non-coding regions, posing significant challenges pinpointing protein-coding genes associated with specific traits. Moreover, growing evidence suggests not all are functional, emphasizing critical need prioritizing causal sites-a task paramount importance biologists. The accumulation publicly available multi-omics data provides an unprecedented opportunity to annotate prioritize QTLs.Therefore, we developed a comprehensive database encompassing four major agricultural species-pig, sheep, cattle, chicken. This integrates accessible datasets, including 140 studies (covering 471 traits), 2,625 QTL datasets (spanning 1,235 86 Hi-C (from 8 cell/tissue types), 95 epigenomic 4 769 transcription factor motifs. aims link GWAS/QTL regions target they regulate, regulatory elements. Ultimately, it resource potential validation targets elucidating molecular pathways economically important traits animals.

Language: Английский

Citations

0
Overcoming collaboration barriers in quantitative trait loci analysis DOI Creative Commons

Wen Zhang,

Xiaohong Wu,

Jing Gong

et al.

Cell Genomics, Journal Year: 2025, Volume and Issue: 5(2), P. 100773 - 100773

Published: Feb. 1, 2025

In this issue of Cell Genomics, Choi et al.1 report a novel approach, privateQTL, which leverages secure multiparty computation (MPC) to enable federated expression quantitative trait loci (eQTL) mapping across institutions without compromising data privacy. Zhang al. preview their approach and discuss its application in future genetic analyses.

Language: Английский

Citations

0
Functional genomics in age-related macular degeneration: From genetic associations to understanding disease mechanisms DOI
Rinki Ratnapriya,

Felix Grassman,

Runsheng Chen

et al.

Experimental Eye Research, Journal Year: 2025, Volume and Issue: 254, P. 110344 - 110344

Published: March 13, 2025

Language: Английский

Citations

0
Whole genome sequencing of 4,787 individuals identifies gene-based rare variants in age-related macular degeneration DOI Creative Commons
Alan Kwong, Matthew Zawistowski, Lars G. Fritsche

et al.

Human Molecular Genetics, Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 2, 2023

Genome-wide association studies have contributed extensively to the discovery of disease-associated common variants. However, genetic contribution complex traits is still largely difficult interpret. We report a genome-wide study 2394 cases and 2393 controls for age-related macular degeneration (AMD) via whole-genome sequencing, with 46.9 million Our reveals significant single-variant signals at four loci independent gene-based in CFH, C2, C3, NRTN. Using data from Exome Aggregation Consortium (ExAC) test, we demonstrate an enrichment predicted rare loss-of-function variants CFI, as-yet unreported gene AMD, ORMDL2. method using large variant list without individual-level genotypes as external reference provides flexible convenient approach leverage publicly available datasets augment search associations, which can explain additional disease risk AMD.

Language: Английский

Citations

5
The Complement Factor H (Y402H) risk polymorphism for age-related macular degeneration affects metabolism and response to oxidative stress in the retinal pigment epithelium DOI

Peng Shang,

Helena M. Ambrosino,

Johnson Hoang

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 225, P. 833 - 845

Published: Nov. 1, 2024

Language: Английский

Citations

1
Single-cell analysis of the epigenome and 3D chromatin architecture in the human retina DOI Creative Commons
Ying Yuan, Pooja Biswas, Nathan R. Zemke

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 29, 2024

Abstract Most genetic risk variants linked to ocular diseases are non-protein coding and presumably contribute disease through dysregulation of gene expression, however, deeper understanding their mechanisms action has been impeded by an incomplete annotation the transcriptional regulatory elements across different retinal cell types. To address this knowledge gap, we carried out single-cell multiomics assays investigate chromatin accessibility, DNA methylome 3D architecture in human retina, macula, pigment epithelium (RPE)/choroid. We identified 420,824 unique candidate characterized states 23 sub-classes cells. Comparative analysis landscapes between mouse retina cells further revealed both evolutionarily conserved divergent gene-regulatory programs. Leveraging rapid advancements deep-learning techniques, developed sequence-based predictors interpret non-coding diseases. Our study establishes retina-wide, transcriptome, epigenome, genome atlases, provides a resource for studying programs relevant

Language: Английский

Citations

1