RGC structure and mitochondrial function in LHON: the paradox of recovery and an extended therapeutic window.

Brief Lay background

Leber hereditary optic nerve neuropathy (LHON) is a rare genetic condition that affects the optic nerve, which sends visual information from the eye to the brain.

Most commonly affecting young adult men, LHON causes a sudden, painless loss of central vision in both eyes. It is caused by faults in the genetic code of mitochondria, which are the tiny ‘powerhouses’ of our cells.

What problem/knowledge gap does it help address

Faults in four different genes have so far been linked with LHON. These genes interfere with the ability of the mitochondria to generate sufficient energy, which leads to the loss of nerve cells in the retina – called retinal ganglion cells (RGCs) – and the subsequent degeneration of the optic nerve.

In most people with LHON, sight loss is permanent. But rarely, some patients can appear to recover some of their vision even many years later. This suggests that not all RGCs are lost – and instead, some may be ‘sleeping’ and could potentially be revived.

Aim of the project

To investigate how apparently sick and dysfunctional RGCs may still be capable of recovery – to establish a scientific basis for the development of new treatments to reverse sight loss in LHON patients.

Key procedures/objectives

The researchers will study two RGC cell models derived from stem cells of patients with LHON – and one mouse model of the disease to:

1. Characterise the molecular and cellular features of RGCs in detail.
2. Study the structure and function of RCGs to look for evidence of surviving sick and dysfunctional RGCs.
3. Determine whether RGCs are capable of spontaneous recovery of their normal function.
4. Test the effects of a drug called idebenone – which is thought to support the mitochondria and is approved in some countries for treating LHON – on RGCs.

Potential impact on people with sight loss

This research could ultimately pave the way for the development of new treatments for people with LHON that offer the hope of reversing their sight loss and improving their quality of life.