Project description:This study compared genome-wide expression profiles of individuals with and without Primary Open-Angle Glaucoma (POAG). One POAG case (case #6 with two replicates #10 and #11) carried a Q368X myocilin mutation. This study compared the genome-wide expression in human trabecular meshwork tissue between 13 controls and 15 POAG cases. Six controls and one POAG cases had the expression performed from both left and right eyes. One technical replicate was done between two cases. The average from the biological replicates for each inidividual was used for analysis.
Project description:The changes in the trabecular meshwork in steroid-induced glaucoma are similar to those in human primary open-angle glaucoma. To explore the changes in the trabecular meshwork in POAG, we extracted RNA from human trabecular meshwork cells with or without dexamethasone, followed by next-generation transcriptome sequencing to observe changes in gene expression in trabecular meshwork cells, thereby better understanding the mechanism of increased IOP.
Project description:MicroRNAs were associated with the development and progression of glaucoma. Our study aims to identify the potential miRNAs and target genes in human trabecular meshwork related to primary open-angle glaucoma (POAG).
Project description:Long non-coding RNAs were associated with the development and progression of glaucoma. Our study aim to identify the potential genes in human trabecular meshwork related to primary open-angle glaucoma (POAG).
Project description:The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes. By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.
Project description:The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes. By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.
Project description:The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes. By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.
Project description:The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes. By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.
Project description:The physiology of trabecular meshwork (TM) controls aqueous humor outflow resistance and thereby intraocular pressure (IOP), a major risk factor for primary open-angle glaucoma (POAG). To decipher how GWAS-identified non-coding variants contribute to IOP and POAG, we generated a high-resolution map of genome topology and regulatory modules from primary human TM cell lines. Integrated analyses with dexamethasone-treated TM cells, a model of augmented IOP, demonstrate extensive changes in chromatin compartments, accessibility, looping, and histone marks that are highly concordant with transcriptional changes. By combining GWAS-associated variants with dexamethasone-induced chromatin looping, we discovered 26 IOP- and 52 POAG- candidate causal genes, belonging to key TM pathways, including integrin, transcriptional regulation of VENTX, and TNF signaling. Our studies provide a mechanistic framework for elucidating genetic complexity of IOP and pathogenesis of POAG and suggest new targets for therapies.
