Seeing the intricate structures and processes that power our vision as they occur in the eye can help scientists develop new treatments to fight disease.

Dr Luis Alarcon-Martinez, Head of Visual neurovascular research at CERA, is using two-photon microscopy techniques to investigate the optic nerve at a scale not previously possible.

“It’s very exciting because this novel microscope’s setup will enable us to see optic nerve fibres damaged by glaucoma in extremely high detail,” says Dr Alarcon-Martinez.

“This will hopefully provide insights into why glaucoma causes this damage in the optic nerve.”

Your optic nerve is like a cable: transmitting electrical signals from the eye to your brain, where they’re interpreted as images. In glaucoma, these signals are disrupted.

The disease attacks the retinal ganglion cells, which make up the optic nerve, leading to vision loss.

It is not known exactly how retinal ganglion cells are damaged in glaucoma, but one of the biggest risk factors is high intraocular pressure (IOP).

Zooming in

While not all patients with glaucoma have high IOP, many show irregularities in the blood vessels of their eyes – something Dr Alarcon-Martinez is keen to investigate.

“A problem we face in glaucoma research is that we don’t have imaging techniques to visualise the optic nerve at very high resolution,” says Dr Alarcon-Martinez.

Two-photon microscopy is an imaging technique that allows the visualisation of living tissue at depths unachievable with other microscopes.

The team recently developed a world-first two-photon microscopy image set up to see the blood flow in the retina of living organisms – leading to the discovery of previously unseen structures.

Thanks to an Australian Vision Research grant, Dr Alarcon-Martinez’s team will now use this technology, combined with special microsurgery techniques, to access the optic nerve in a living organism.

They will then attempt to compare the blood flow in a healthy optic nerve against that of a glaucoma-affected optic nerve.

“Two-photon technology has been around for a long time, however, we are the first to adapt it for these purposes,” says Dr Alarcon-Martinez.

Hope for gene therapy

Dr Alarcon-Martinez says, if successful, the insights provided by the imaging could be applied to future trials of gene therapies such as those being developed by Professor Keith Martin, CERA Managing Director and Head of Glaucoma Research.

Professor Martin is leading a collaboration between the University of Melbourne and the University of Cambridge to investigate potential gene therapies to strengthen the optic nerve and protect it from damage.

To achieve this, the research team are studying a molecule that may hold the answer to improving the ‘transport system’ within the nerve fibres of the eye.

Professor Martin says he is excited by the potential this imaging technique could offer.

“The ability to visualise the optic nerve in such high detail may enable us to better understand how the optic nerve degenerates in glaucoma and how it can be repaired,” he says.

“In turn, this could help us determine which gene therapies are most likely to be effective in human clinical trials.”

Broader impact

While in its early stages, the research could provide preliminary data that may one day lead to developing therapies that preserve optic nerve health – and support existing strategies for lowering intra-ocular pressure.

“If we’re successful, it could have a huge impact on glaucoma and other diseases related to the optic nerve,” says Dr Alarcon-Martinez.

This includes other eye diseases such as age-related macular degeneration, as well as many neurodegenerative diseases such as Alzheimer’s and Amyotrophic lateral sclerosis, the most common form of motor neuron disease.

Dr Alarcon-Martinez says hopefully in the future the technology could help assess the impact of trauma on vision.

“We may even be able to examine the eye injuries suffered by military personnel who have received trauma to their optic nerve caused by explosions.”