Targeting NAD+ for retinal ganglion cell protection in experimental glaucoma
- Type of funding: PhD Studentship
- Grant Holder: Professor James Morgan
- Institute: Cardiff University
- Region: Wales
- Start date: October 2019
- End Date: December 2022
- Priority: Prevention
- Eye Category: Glaucoma
Brief Lay Background
Glaucoma is a collective term for a group of diseases that cause irreversible sight loss. Glaucoma affects ~80 million people globally, and with an aging population this is set to increase to 120 million people by 2040.
Current treatments aim to reduce elevated eye pressure. These range from eye drops to surgery that allows fluid drainage and relieves eye pressure. There is an urgent need to develop new treatments that stop the damage caused by elevated eye pressure from progressing to glaucoma.
What problem/knowledge gap does it help address
Professor Morgan’s team has previously shown in mice that a new drug called nicotinamide (NAM) can prevent damage to nerve cells called retinal ganglion cells. These nerve cells connect signals received by the retina of the eye to the brain. They are often damaged in the early stages of glaucoma. NAM is a precursor to a substance called NAD, which is important for many functions in cells.
The effects of NAM on glaucoma in mice have led to initial clinical trials to explore the potential of NAM in patients with glaucoma. However, there is still unanswered questions about the optimal timing and dose of NAM treatment. This study will explore the timing of nerve cell damage in mice with glaucoma and how, and when, NAM protects against this damage. The PhD student will also look at whether using gene therapy to increase levels of NAM in the eye can boost its therapeutic effects without causing side effects in the rest of the body.
Aim of the research project
The project aims to:
- Measure the sequence of small changes that occur to nerve cells in the retina over time because of elevated eye pressure.
- Assess how these changes are altered following treatment with NAM at different doses, either alone or in combination with gene therapy.
This award will also contribute to building capacity in glaucoma research as it will lead to a PhD for an early career researcher.
The PhD student will study mice with elevated eye pressure that leads to glaucoma to:
- Understand how damage to the retinal ganglion nerve cells in mice with glaucoma affects their connectivity with other nerve cells that transmit visual information to the brain.
- Measure the effect of three different doses of NAM treatment on damage to nerve cells in the retina.
- Assess whether gene therapy that switches on NAM production is effective at preventing damage in mice with glaucoma, alone or in combination with NAM treatment.
- Test whether combining NAM or Nam and gene therapy works in mice that are also being given medicine to lower eye pressure, to mirror the way patients with glaucoma are currently treated.
Potential impact on people with sight loss
The results from this study will help to determine the optimal NAM dose for preventing pressure-induced damage in mice with glaucoma. It will also reveal whether gene therapy has additional benefits over and above NAM treatment alone. This information can be used in ongoing and new clinical trials testing NAM as a new treatment for people with glaucoma.