ArticleHuman molecular genetics2024
High throughput functional profiling of genes at intraocular pressure loci reveals distinct networks for glaucoma.
Article in Human molecular genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Deletion of ARPKD-associated Pkhd1 gene in mice results in decreased Tfap2b expression and eye abnormalities.Nature communications · 2026Article
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- Insights from pooled CRISPRi single-cell screens in K562 cells reveal gene functions, regulatory networks, and highlight opportunities and limitations.BMC genomics · 2026Article
- Uncovering the Genetic Architecture of Optic Nerve Integrity Estimates through Genome-wide Association Study Meta-analyses.medRxiv : the preprint server for health sciences · 2026Article
- Large scale compound selection guided by cell painting reveals activity cliffs and functional relationships.Communications biology · 2026Article
- Applications of single-cell transcriptomics in glaucoma research: from the aqueous humor outflow pathway to retinal ganglion cell neurodegeneration.Frontiers in physiology · 2026Review
- iPSC-derived ITGA6-positive cells restore aqueous humor outflow in glaucoma eyes.Nature communications · 2025Article
- Cross-Tissue Transcriptome-Wide Association Study Identifies Novel Genes Associated With POAG.Investigative ophthalmology & visual science · 2025Article
- Recent Advancements in Understanding the Role and Mechanisms of Angiopoietin-like Proteins in Diabetic Retinopathy.Metabolites · 2025Review
- Potential Functions and Causal Associations of GNLY in Primary Open-Angle Glaucoma: Integration of Blood-Derived Proteome, Transcriptome, and Experimental Verification.Journal of inflammation research · 2025Article
- Epigenetics in Glaucoma.Medicina (Kaunas, Lithuania) · 2024Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 1 country.
Funding
Abstract
introductionPrimary open angle glaucoma (POAG) is a leading cause of blindness globally. Characterized by progressive retinal ganglion cell degeneration, the precise pathogenesis remains unknown. Genome-wide association studies (GWAS) have uncovered many genetic variants associated with elevated intraocular pressure (IOP), one of the key risk factors for POAG. We aimed to identify genetic and morphological variation that can be attributed to trabecular meshwork cell (TMC) dysfunction and raised IOP in POAG.
methods62 genes across 55 loci were knocked-out in a primary human TMC line. Each knockout group, including five non-targeting control groups, underwent single-cell RNA-sequencing (scRNA-seq) for differentially-expressed gene (DEG) analysis. Multiplexed fluorescence coupled with CellProfiler image analysis allowed for single-cell morphological profiling.
resultsMany gene knockouts invoked DEGs relating to matrix metalloproteinases and interferon-induced proteins. We have prioritized genes at four loci of interest to identify gene knockouts that may contribute to the pathogenesis of POAG, including ANGPTL2, LMX1B, CAV1, and KREMEN1. Three genetic networks of gene knockouts with similar transcriptomic profiles were identified, suggesting a synergistic function in trabecular meshwork cell physiology. TEK knockout caused significant upregulation of nuclear granularity on morphological analysis, while knockout of TRIOBP, TMCO1 and PLEKHA7 increased granularity and intensity of actin and the cell-membrane.
conclusionHigh-throughput analysis of cellular structure and function through multiplex fluorescent single-cell analysis and scRNA-seq assays enabled the direct study of genetic perturbations at the single-cell resolution. This work provides a framework for investigating the role of genes in the pathogenesis of glaucoma and heterogenous diseases with a strong genetic basis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.