miRNA-mediated therapy for the treatment of glaucoma

Brief Lay Background

The back of the eye is known as the retina and is responsible for transmitting information derived from light to the brain. Ultimately, it allows humans to see. Of particular importance is one cell type, the retinal ganglion cell (RGC). The RGC is what makes up the optic nerve and is solely responsible for connecting the eye to the brain. Its loss is always associated with irreversible blindness. Various diseases are characterized by the loss of RGC and include traumatic optic neuropathy and glaucoma. Notably, glaucoma currently affects 80 million people and an estimated 120 million by 2040. RGC loss is often used as a simplified model of other CNS injuries, and experimental treatments for spinal cord injury are often first tested in the eye.

Of recent interest as a therapy are small, naturally occurring molecules known as "miRNA". miRNA act by inhibiting the synthesis of proteins and work to control and regulate the protein levels in all of our cells. The levels of proteins in a cell are thus determined by the actions of miRNA, and they can be considered important regulators of cell health. Equally, in disease states, these regulators fail, which leads to disease progression. While much research interest has been given to the delivery of proteins, little has been given to understanding miRNA. This can be explained by the complexity of miRNA, with each miRNA potentially blocking thousands of different protein synthesis pathways. This complexity opens up great potential, with modulating miRNA having a potentially widespread effect on the protein landscape of a cell.

What problem/knowledge gap does it help address

There is no available neuroprotective treatment for RGC loss diseases such as glaucoma, and research has demonstrated that there is unlikely to ever be a "magic bullet" style treatment where a single drug with a single target is efficacious in this highly complex disorder.

Aim of the research project

This study will seek to generate the first complete profile of miRNA changes in RGC, before and after injury, and use this information to identify candidate miRNA for treatment.

Key procedures/objectives

1. Develop models for glaucoma and another eye disease, traumatic optic nerve damage.
2. Use the models to isolate the miRNA at different timepoints in the diseases.
3. Identify candidate miRNA and analyse visual function across different conditions.
4. Compare the profile candidate miRNA to miRNA in RGC to assess translational potential.

Potential impact on people with sight loss

The researchers aim to have a candidate list of miRNA that are involved, and potentially causative in retinal degeneration and blindness, but will also have tested some of these candidates and identified a successful treatment. miRNA therapy is still in its infancy and thus this project may yield novel new drugs that can then be tested in clinical trials.