Oral Presentation 47th Lorne Genome Conference 2026

Single cell transcriptional profiling of primary trabecular meshwork cells uncovers genetic drivers of glaucoma. (134362)

Alex W Hewitt 1 , Alexander Barnett 1 , Thomas Guinan 1 , Freya Patterson 1 , Sandy Hung 2 , Helena Liang 2 , Stuart MacGregor 3 , Jamie Craig 4 , Rajendra KC 1 , Kirsten Fairfax 1
  1. University of Tasmania, Hobart, TAS, Australia
  2. Centre for Eye Research Australia, Melbourne, VIC, Australia
  3. Queensland Institute of Medical Research, Brisbane, Queensland, Australia
  4. Flinders University of South Australia, Adelaide, South Australia, Australia

Elevated intraocular pressure (IOP) is currently the sole modifiable risk factor for glaucoma, a leading cause of irreversible blindness worldwide. The trabecular meshwork (TMW) plays a pivotal role in regulating IOP by facilitating aqueous humour outflow. We performed single cell expression quantitative trait loci (eQTL) mapping in TMW cells collected from 74 people (45 males, 29 females) donors. Following isolation and culture with or without dexamethosone, a total of 316,799 singlet cells were captured and underwent RNA sequencing. Differential gene expression analysis revealed 63 upregulated (log2 fold change >3) and 17 downregulated (log2 fold change >3) genes following dexamethasone exposure. A total of 164,378 cis acting eSNPs and 6,178 eGenes were identified. The causal variants at several IOP and glaucoma-associated loci were definitively mapped using colocalization. Understanding the genetic underpinnings of IOP regulation through an improved understanding of the molecular pathways involved in TMW homeostasis will facilitate novel therapeutic development.