Developing molecular therapies for glaucoma using an ex vivo human organ culture system

Primary open angle glaucoma is a major cause of visual morbidity affecting more than 60 million individuals worldwide; and the second most common cause of blindness in the world: resulting in bilateral blindness in 4.5 million people. Elevated intraocular pressure (IOP) is a major risk factor for developing glaucoma. Animal models have formed an integral part of research into glaucoma pathogenesis, and to determine the efficacy of therapeutic interventions to control intra-ocular pressure. The most representative non-human glaucoma models are primates but there are a number of ethical and economic reasons which make this a difficult model for most glaucoma research groups to utilise. The principal aim of this studentship is to establish an ex vivo human organ culture system glaucoma model and to use this model to evaluate the therapeutic potential of manipulating transforming growth factor-ß (TGF-ß) signalling in glaucoma. This disease model recapitulates the disease phenotype in the human eye and downstream experiments are performed in human tissue. Glaucoma pathogenesis involves increased aqueous humor outflow resistance, a result of several morphologic and biochemical changes in the trabecular meshwork. This project aims to evaluate the potential of TGF-ß blocking peptides and siRNAs in the management of IOP as a therapeutic intervention for glaucoma. The human organ culture system glaucoma model recapitualtes the in vivo human disease. It is anticipated that this project will lead to the wider adoption of this glaucoma model by other research groups in both academia and industry which would significantly broaden the impact of this project and represent a significant further replacement or reduction in animal use within the wider research community.

Kathirvel K et al. (2022). Short and long-term effect of dexamethasone on the transcriptome profile of primary human trabecular meshwork cells in vitro. Scientific Reports 12: e8299. doi: 10.1038/s41598-022-12443-7