title: The role of epigenetics in the fibrotic processes associated with glaucoma.
abstract: Glaucoma is an optic neuropathy that affects 60 million people worldwide. The main risk factor for glaucoma is increased intraocular pressure (IOP), this is currently the only target for treatment of glaucoma. However, some patients show disease progression despite well-controlled IOP. Another possible therapeutic target is the extracellular matrix (ECM) changes in glaucoma. There is an accumulation of ECM in the lamina cribrosa (LC) and trabecular meshwork (TM) and upregulation of profibrotic factors such as transforming growth factor β (TGF β ), collagen1 α 1 (COL1A1), and α -smooth muscle actin ( α SMA). One method of regulating fibrosis is through epigenetics; the study of heritable changes in gene function caused by mechanisms other than changes in the underlying DNA sequence. Epigenetic mechanisms have been shown to drive renal and pulmonary fibrosis by upregulating profibrotic factors. Hypoxia alters epigenetic mechanisms through regulating the cell's response and there is a hypoxic environment in the LC and TM in glaucoma. This review looks at the role that hypoxia plays in inducing aberrant epigenetic mechanisms and the role these mechanisms play in inducing fibrosis. Evidence suggests that a hypoxic environment in glaucoma may induce aberrant epigenetic mechanisms that contribute to disease fibrosis. These may prove to be relevant therapeutic targets in glaucoma.
authors.affiliation: UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Fiona
authors.identifier: 0000-0001-7563-7258
authors.initials: F
authors.lastname: McDonnell
authors.affiliation: UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland ; Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Colm
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: UCD School of Medicine and Medical Science, University College Dublin, Dublin, Ireland ; Department of Ophthalmology, Mater Misericordiae University Hospital, Dublin, Ireland.
authors.forename: Deborah
authors.identifier: 0000-0003-2363-106X
authors.initials: D
authors.lastname: Wallace