UKEGS 2016

Professor Paul Foster

UCL Institute of Ophthalmology, London

Project Title: Enhanced, Repeat Imaging of UK Biobank Participants

Amount awarded: £35,375.00

Length of Project:  late 2017 to late 2019

 

Purposes of the project

To support the collection of macular optical coherence tomography data and digital retinal photographs in 10,000 UK Biobank participants aged 50 to 79 years undergoing repeat indepth

imaging, including brain, heart and abdominal MRI, carotid ultrasound and whole body DEXA scans.

To lay the foundations for ground-breaking longitudinal studies of the eye in health and disease, and the association of ophthalmic characteristics with multi-system and systemspecific disease in later life.

To build translational research capacity, contributing newly created data to the open access UKBB data repository, making it available to other researchers in academic and industrial sectors in the UK and globally.

 

Professor Keith Martin

Cambridge                                                                                                                                 

Project Title: Axon regeneration of human retinal ganglion cells

Amount awarded: £34,625.00

Length of Project: 12 months from May 2017 to May 2018

Objectives

The optic nerve is composed of nerve fibres (axons) from retinal ganglion cells (RGCs) which carry visual signals to the brain. Once damaged, axons cannot regenerate and deficits in vision are permanent. Our objective is to assess whether regeneration strategies to stimulate regrowth of rodent RGC axons following optic nerve crush injury (ONC) are translatable and can stimulate human RGC axon regeneration. Our long term goal is to develop new treatments for patients with severe glaucoma where vision has been lost despite conventional treatment and ultimately reverse loss of sight.  

Methodology

We have developed an ex-vivo human retinal explant model using post mortem tissue, providing a unique method to study human RGC responses to treatments (Osbourne A, et al 2016). We will infect human RGCs with viruses that deliver and alter genes (PTEN and IL-6) known to play a role in rodent RGC axon regeneration.

Recent work

Knockout of the PTEN gene in mutant mice results in RGC axon regeneration following ONC, an effect mediated by enhanced mTOR signalling (Park KK, et al 2008). Our collaborator, Zhigang He, has developed a viral vector that selectively knocks down PTEN in wildtype tissue that stimulates mouse DRG neurones regeneration in a spinal cord injury model (Zukor K, et al 2013). We have been testing this construct and can demonstrate that it also stimulates mouse RGC axon regeneration following ONC.  In addition, we have a virus that delivers hyperactive IL-6 into RGCs which stimulates mouse RGC axon regeneration via Jak/STAT signalling activation (Leibinger M, et al 2016). We plan to assess whether these regeneration stimuli can promote re-growth of human RGC axons.

Significance & Impact

Current clinical therapies for glaucoma and neuroprotective strategies that are in development aim solely to slow the progression of the disease without restoring vision. However, over 10% of glaucoma patients (>7 million people) become blind because of late presentation and/or aggressive disease progression despite treatment and yet less than 10% of nerve fibres are sufficient to maintain functional central vision in many patients. Restoring this relatively small proportion could make the difference between preserved central vision and blindness. This study provides proof of principle of whether human optic nerve regeneration is possible.