Chromatin maps of dexamethasone-treated eye cells link 67 genes to high eye pressure and glaucoma
In cultured human trabecular meshwork cells, dexamethasone-induced chromatin changes were matched to GWAS variants for intraocular pressure and primary open-angle glaucoma.
Researchers modeled elevated intraocular pressure (IOP) by treating three primary human trabecular meshwork cell strains with dexamethasone, according to a study in Proceedings of the National Academy of Sciences pnas.org
Proceedings of the National Academy of Sciencespnas.orgOpen source ↗. Primary open-angle glaucoma (POAG) is a chronic neurodegenerative disorder, and elevated IOP is its only modifiable risk factor. The authors generated a high-resolution map of promoter-centered chromatin contacts and regulatory modules in these cells.
They report dynamic changes in chromatin compartments and looping, cis-regulatory elements and transcription factor hubs, matching altered expression profiles. Combining genome-wide association study variants with the dexamethasone-induced chromatin landscape, the authors linked 29 target genes to 23 lead IOP variants and 57 genes to 46 POAG variants; 19 genes are shared.
Pathway analysis of the 67 IOP- and POAG-associated genes showed enrichment in vesicle transport, TLR, MAPK and hippo-YAP signaling. The authors also report a transcriptional regulatory role for 103 noncoding lead variants. They describe the results as a mechanistic framework for the genetics of steroid-induced IOP and related POAG pathology.
