Investigating how brain-derived neurotrophic factor (BDNF) could prevent cell death in glaucoma

Brief lay background

Glaucoma is the leading cause of irreversible blindness worldwide. Current treatments are aimed at the reduction of intraocular pressure (IOP) as this is the only modifiable risk factor. However, many patients continue to lose sight despite effective IOP control highlighting a pressing need to find additional treatments. Glaucoma is characterised by the degeneration and loss of retinal ganglion cells (RGCs).

These nerve cells are responsible for transmitting signals from the light-sensitive photoreceptors in the retina to the brain. Preserving the RGCs with neuroprotective agents may therefore be a good strategy to prevent further sight loss. An ideal candidate for this is Brain-Derived Neurotrophic Factor (BDNF) which has been shown to have neuroprotective effects on RGCs as well as many other types of nerve cells.

Unfortunately, BDNF can be challenging to use therapeutically and the beneficial effects are reduced if exposure is prolonged. Finding novel delivery mechanisms and ways to control it have therefore become a key focus of BDNF research.

What problem/knowledge gap does it help address

One novel solution to these problems is to access a large, existing store of BDNF within platelets. These platelets can be activated using ultrasound, which could be applied to facilitate regional release of BDNF. The team will explore the use of ultrasound induced BDNF release as a targeted treatment for glaucoma.

Aim of the research project

To determine if BDNF can be released in a controlled way from platelets when stimulated with ultrasound and prevent the degeneration of RGCs in a model of glaucoma.

Potential impact on people with sight loss

Achieving these goals will help demonstrate how BDNF can be used as a treatment. This could bring researchers closer to a viable clinical treatment by addressing several of the difficulties in delivery and dose control.

The direct protection of RGCs could allow a novel method of treating glaucoma that could work in conjunction with current strategies controlling IOP. In addition, ultrasound delivery is safe and cost effective, ensuring a fast route to clinical deployment should  the study be successful. This is particularly important when damage to the optic nerve caused by glaucoma is currently irreversible.