Revolutionary technology offers new hope to people with glaucoma, retinitis and macular degeneration

In January 2009, the life of the engineer Michel Meunier, a professor at Polytechnique Montréal, changed dramatically. Like others, he had observed that the extremely short pulse of a femtosecond laser (0.000000000000001 seconds) could reveal nanometer-sized holes in silicon coated with gold nanoparticles. But this researcher, internationally recognized for his skills in laser and nanotechnology, decided to go further with what was then a laboratory curiosity. He wondered if it was possible to switch from silicon to living matter, from inorganic to organic. Could the nanoparticles of gold and the femtosecond laser, this "light scalpel", reproduce the same phenomenon with living cells?

Professor Meunier began working on cells in vitro in his Polytechnic laboratory. The challenge was to perform a nanometric incision in the extracellular membrane of the cells without damaging it. Using gold nanoparticles that act as "nanolenses", Professor Meunier realized that it was possible to focus the light energy from the laser to a length of ## 148 ## 800-nanometer wave. Since the cells absorb very little energy at this wavelength, their integrity is preserved. Mission accomplished!

On the basis of this discovery, Professor Meunier decided to work on cells in vivo, cells being part of a complex living cell structure, such as the eye, for example.

The eye and the light scalpel

In April 2012, Professor Meunier met Przemyslaw Sapieha, an internationally renowned eye specialist, who is particularly known for his work on the retina. "Mike," he says, is a professor in the Department of Ophthalmology at the University of Montreal and a researcher at the Integrated Health and Social Services Center (ICSUS) of East-Island. 39, Montreal Island. He immediately understood the potential of this new technology and everything that could be done in the eyes if you could block the effect of workout resulting from a trigger leading to glaucoma or macular degeneration for example by injecting drugs, proteins or even genes.

The use of a femtosecond laser to treat the eyes – a highly specialized and fragile organ – is however very complex. The eye is part of the central nervous system. As a result, many of the cells or families of cells that compose it are neurons. And when a neuron dies, it does not regenerate like other cells do. So Mike Sapieha's first task was to make sure that a femtosecond laser could be used on one or more neurons without affecting them. This is called "proof of concept".

Proof of concept

Mike and Michel have engaged Ariel Wilson, a biochemistry researcher, specialist in eye structures and vision mechanisms, as well as Professor Santiago Costantino and his team at the Department of Ophthalmology of the Université de Montréal and the CIUSSS of East-Island-of-Montreal for its expertise in biophotonics. The team first decided to work on healthy cells because they are better understood than sick cells. They injected gold nanoparticles combined with antibodies to target specific neuronal cells in the eye, and then waited for the nanoparticles to settle around various neurons or families of neurons, such as the retina. Following the bright flash generated by the femtosecond laser, the expected phenomenon has occurred: small holes appeared in the retina cells of the eye, allowing to effectively inject drugs or genes in specific areas of the eye. A new victory for Michel Meunier and his collaborators. These conclusive results now open the door to new treatments.

The technology developed by Polytechnique and CIUSSS researchers from the East-Island of Montreal is characterized by extreme precision. With the use of functionalized gold nanoparticles, the lightweight scalpel can accurately locate the family of cells where the doctor will need to intervene.

After successfully demonstrating the proof of concept, Professor Meunier and his team filed a patent application in the United States. This remarkable work was also the subject of an article reviewed by an impressive reading committee and published in the famous journal Nano Letters in October 2018.

Although there is still a lot of research to be done – for at least 10 years, first on animals, then on humans – this technology could make all the difference for an aging population suffering from deterioration of the eyes for which there are still no effective long-term treatments. It also has the advantage of avoiding the use of viruses commonly used in gene therapy. These researchers are studying the applications of this technology in all eye diseases, but more particularly in glaucoma, retinitis and macular degeneration.

This lightweight scalpel is unprecedented.