Unblocking the drain to lower eye pressure

Research details

  • Type of funding: PhD Studentship
  • Grant Holder: Professor Colin Willoughby
  • Institute: University of Liverpool
  • Region: North West
  • Start date: October 2016
  • End Date: September 2019
  • Priority: Causes
  • Eye Category: Glaucoma


Primary open-angle glaucoma is the leading cause of blindness worldwide. An important risk for this type of glaucoma is high pressure in the eye as this can damage the optic nerve (which sends visual information from eye to brain).

High eye pressure happens when it becomes harder than usual for the fluid that fills the eye (aqueous humour) to drain away. In a healthy eye there is a balance between the rate at which the eye makes and drains the fluid.

Current glaucoma drug treatments focus on lowering eye pressure by making the eye produce less aqueous humour. They don’t target the fact that it’s harder to drain (outflow resistance) the eye, which means the root cause is still there and the condition can get worse.

In this project the student will be looking at a substance that helps control the connective tissue scaffolding around cells in the eye’s drainage system. They are trying to find a potential drug treatment that could change it so that aqueous humour can drain away well again, as this could slow or stop glaucoma from progressing.
  • Scientific summary

    Unravelling the molecular mechanism of connective tissue growth factor (CCN2) in glaucoma.

    Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide, and intraocular pressure (IOP) is an important modifiable risk factor. Elevated IOP in POAG is due to increased resistance to aqueous humour outflow resulting from increased extra-cellular matrix (ECM) in the trabecular meshwork (TM). None of the current pharmacological glaucoma treatments target the outflow resistance and ECM changes in the TM, rather they target the disease from the aqueous production side. These treatment approaches do not therefore halt the progressive molecular pathology in the TM, and so aqueous outflow resistance and IOP continue to increase, requiring further intervention.

    Elevated levels of transforming growth factor β (TGFβ) in the aqueous humour bathing the TM has been shown to alter ECM production, and is an important player in the pathogenesis of glaucoma. Inhibiting TGFß as a treatment option is deleterious and counter effective as TGFβ has multiple other roles on different cells within the same organ. Connective tissue growth factor, also known as CCN2, a downstream mediator of TGFß, presents a better option for therapy. Conditional CCN2 over-expression transgenic mouse models will be used to dissect the contribution of CCN2 in the development and progression of glaucoma and the influence of exogenous TGFβ. CCN2 expression will then be manipulated and evaluated in human and animal glaucoma models using microRNA (miRNA) based therapeutics. These data will raise the possibility for a new class of disease-modifying therapeutics using miRNA biology to halt/slow disease progression.