Investigating the influence of life-long metabolic factors that contribute to age-related sight loss conditions

Brief lay background

Glaucoma is caused by a combination of adverse external factors, increasing age, and inherited genetic susceptibility. Genetic studies have identified hundreds of small genetic changes causing susceptibility to glaucoma, enabling us to understand some mechanisms involved.

However genetic risk factors cannot be changed, and novel treatments can only indirectly target the pathways causing disease. Much of glaucoma risk is caused by non-heritable, or “environmental” factors. These, and genetic factors often result in changes in metabolites, which are chemicals found in blood and eye tissues and are involved in biological and metabolic processes.

What problem/knowledge gap does it help address

The understanding of mechanisms underlying glaucoma (and other age-related diseases), has improved dramatically, in large part due to the progress made through investigations of the genetic basis of the disease.

For all its undisputed usefulness, the translation pathway into bedside care is long and arduous. This is partly due to the difficulty in linking genetic predisposition to actual damage in the relevant parts of the eye.

Metabolomics is a relatively new scientific discipline where single metabolites are used as markers of cell and tissue health and statistically compared with the disease status in a population.

Aim of the research project

To identify changes in metabolism that lead to glaucoma which could result in new treatments.

Key procedures/objectives

1. Identify metabolites in the UK Biobank in relationship to glaucoma risk.
2. Investigate novel factors that are not in the UK Biobank.
3. Identify key metabolites that are likely to cause glaucoma and may be likely targets to potential therapies.

Potential impact on people with sight loss

This project will further contribute to the understanding of what links disease predisposing genetic factors and metabolism to glaucoma. In addition to generating new information about glaucoma, the study is likely to provide potentially translatable knowledge, as metabolic pathways are particularly amenable to pharmacological intervention and modification.