Gene therapy may help prevent vision loss from genetic eye disease

Researchers in Ireland have developed a new gene therapy treatment that may be able to save the vision of patients with a genetic disease that can lead to blindness. The condition, known as dominant optic atrophy (DOA), currently has no preventative or cure, but in tests in mice and human cells the team was able to slow progression of the disease.

An inherited condition, DOA usually shows its first symptoms during childhood, as the optic nerves of patients begin to degrade. That results in some vision loss and problems perceiving color, with some patients going completely blind over time.

One of the main root causes of the disease has been identified as a mutation in a gene called OPA1. This gene codes for a protein that maintains function in the mitochondria, the structures that produce energy in cells. Without the OPA1 protein, the mitochondrial network is disrupted and their function weakens. As such, it’s not just vision that suffers – many DOA patients develop other nerve problems.

The new study, involving researchers at Trinity College Dublin, Mater Hospital and the Royal Victoria Eye and Ear Hospital, describes a new gene therapy that could potentially treat DOA. The researchers packaged an mRNA of the OPA1 gene into a harmless virus, which would act as a vehicle to deliver the therapy to the intended target.

In cells mitochondria, highlighted in gold, should form healthy networks (left), but in DOA patients they can become fragmented (right)
In cells mitochondria, highlighted in gold, should form healthy networks (left), but in DOA patients they can become fragmented (right)

Professor Jane Farrar and Dr Daniel Maloney, Trinity College Dublin

This technique was tested in mice that had dysfunctional mitochondria, and were beginning to see their retinal ganglion cells degenerate. Sure enough, the treatment helped boost the function of the affected mitochondria, and prevent cell damage. That in turn protected the animals’ spatial vision.

The team also found that in tests on human cells in culture that were derived from DOA patients, the technique appeared to improve mitochondrial function. That raises hopes that the gene therapy may also end up being a possible treatment for other related diseases as well as DOA.

“OPA1 mutations are involved in DOA and so this OPA1-based therapeutic approach is relevant to DOA,” says Jane Farrar, co-lead author of the study. “However mitochondrial dysfunction is implicated in many neurological disorders that collectively affect millions of people worldwide. We think there is great potential for this type of therapeutic strategy targeting mitochondrial dysfunction to provide benefit and thereby make a major societal impact.”

The research was published in the journal Frontiers in Neuroscience.

Source: Trinity College Dublin

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