Epigenetics in the pathogenesis of pseudoexfoliation glaucoma

Glaucoma is a common cause of blindness, which affects approximately 60 million people worldwide. There are many causes and risk factors for developing this disease but pseudoexfoliation (PXF) syndrome is currently the single most important identifiable risk factor for developing glaucoma (PXFG). A build up of certain proteins (extracellular matrix) also plays a significant role by causing a stiffening (fibrosis) of tissue in the eye. Genetic studies have identified a gene called lysyl oxidase-like 1 (LOXL1) which is thought to be important for an individuals'predisposition to developing this syndrome. Studies have shown that levels of LOXL1 can vary between normal and disease patients and also in disease progression and that there is an increase in fibrosis in the eyes of patients with PXFG. Other factors can also play a role in determining if an individual develops glaucoma, for example levels of hypoxia (lack of oxygen) in the eye. In this study we wish to answer the question of how levels of LOXL1 are altered as glaucoma develops and progresses. We will achieve this by examining a mechanism of controlling LOXL1 expression and fibrosis called epigenetics. This method of regulating the expression of a gene can be switched on in cells exposed to a hypoxic environment such as that present in glaucoma. In this study we will investigate the different forms of the LOXL1 gene (single nucleotide polymorphisms), levels of LOXL1 in cells from donors with and without glaucoma, and cells from normal donors grown in very low levels of oxygen (hypoxia) to determine the role of epigenetics in controlling LOXL1 expression as well as a driver of tissue stiffening (TGF?1) in glaucoma.

Award Date
30 June 2017
Award Value
Principal Investigator
Dr Deborah Wallace
Host Institution
University College Dublin
Investigator Led Projects