Tag Archives: macular degeneration

World’s first liquid retina prosthesis

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The new artificial liquid retina is biomimetic and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors. Credit: IIT-Istituto Italiano di Tecnologia [image downloaded from https://www.medgadget.com/2020/06/injectable-liquid-prosthesis-to-treat-retinal-diseases-developed.html]

A June 29, 2020 news item on Nanowerk announces the world’s first liquid retina prosthesis,

Researchers at IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) has led to the revolutionary development of an artificial liquid retinal prosthesis to counteract the effects of diseases such as retinitis pigmentosa and age-related macular degeneration that cause the progressive degeneration of photoreceptors of the retina, resulting in blindness.

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The multidisciplinary team is composed by researchers from the IIT’s Center for Synaptic Neuroscience and Technology in Genoa coordinated by Fabio Benfenati and a team from the IIT’s Center for Nano Science and Technology in Milan coordinated by Guglielmo Lanzani, and it also involves the IRCCS Ospedale Sacrocuore Don Calabria in Negrar (Verona) with the team lead by Grazia Pertile, the IRCCS Ospedale Policlinico San Martino in Genoa and the CNR in Bologna. The research has been supported by Fondazione 13 Marzo Onlus, Fondazione Ra.Mo., Rare Partners srl and Fondazione Cariplo.

The study represents the state of the art in retinal prosthetics and is an evolution of the planar artificial retinal model developed by the same team in 2017 and based on organic semiconductor materials (Nature Materials 2017, 16: 681-689).

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A June 30, 2020 IIT-Istituto Italiano di Tecnologia (Italian Institute of Technology) press release (also on EurekAlert but published June 29, 2020) provides more detail,

The “second generation” artificial retina is biomimetic, offers high spatial resolution and consists of an aqueous component in which photoactive polymeric nanoparticles (whose size is of 350 nanometres, thus about 1/100 of the diameter of a hair) are suspended, going to replace the damaged photoreceptors.

The experimental results show that the natural light stimulation of nanoparticles, in fact, causes the activation of retinal neurons spared from degeneration, thus mimicking the functioning of photoreceptors in healthy subjects.

Compared to other existing approaches, the new liquid nature of the prosthesis ensures fast and less traumatic surgery that consist of microinjections of nanoparticles directly under the retina, where they remain trapped and replace the degenerated photoreceptors; this method also ensures an increased effectiveness.

The data collected show also that the innovative experimental technique represents a valid alternative to the methods used to date to restore the photoreceptive capacity of retinal neurons while preserving their spatial resolution, laying a solid foundation for future clinical trials in humans. Moreover, the development of these photosensitive nanomaterials opens the way to new future applications in neuroscience and medicine.

“Our experimental results highlight the potential relevance of nanomaterials in the development of second-generation retinal prostheses to treat degenerative retinal blindness, and represents a major step forward” Fabio Benfenati commented. “The creation of a liquid artificial retinal implant has great potential to ensure a wide-field vision and high-resolution vision. Enclosing the photoactive polymers in particles that are smaller than the photoreceptors, increases the active surface of interaction with the retinal neurons, allows to easily cover the entire retinal surface and to scale the photoactivation at the level of a single photoreceptor.”

“In this research we have applied nanotechnology to medicine” concludes Guglielmo Lanzani. “In particular in our labs we have realized polymer nanoparticles that behave like tiny photovoltaic cells, based on carbon and hydrogen, fundamental components of the biochemistry of life. Once injected into the retina, these nanoparticles form small aggregates the size of which is comparable to that of neurons, that effectively behave like photoreceptors.”

“The surgical procedure for the subretinal injection of photoactive nanoparticles is minimally invasive and potentially replicable over time, unlike planar retinal prostheses” adds Grazia Pertile, Director at Operating Unit of Ophthalmology at IRCCS Ospedale Sacro Cuore Don Calabria. “At the same time maintaining the advantages of polymeric prosthesis, which is naturally sensitive to the light entering the eye and does not require glasses, cameras or external energy sources.”

The research study is based on preclinical models and further experimentations will be fundamental to make the technique a clinical treatment for diseases such as retinitis pigmentosa and age-related macular degeneration.

Here’s a link to and a citation for the paper,

Subretinally injected semiconducting polymer nanoparticles rescue vision in a rat model of retinal dystrophy by José Fernando Maya-Vetencourt, Giovanni Manfredi, Maurizio Mete, Elisabetta Colombo, Mattia Bramini, Stefano Di Marco, Dmytro Shmal, Giulia Mantero, Michele Dipalo, Anna Rocchi, Mattia L. DiFrancesco, Ermanno D. Papaleo, Angela Russo, Jonathan Barsotti, Cyril Eleftheriou, Francesca Di Maria, Vanessa Cossu, Fabio Piazza, Laura Emionite, Flavia Ticconi, Cecilia Marini, Gianmario Sambuceti, Grazia Pertile, Guglielmo Lanzani & Fabio Benfenati. Nature Nanotechnology (2020) DOI: https://doi.org/10.1038/s41565-020-0696-3 Published: 29 June 2020

This paper is behind a paywall.

Non-viral ocular gene therapy with gold nanoparticles and femtosecond lasers

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I love the stylistic choice the writer made (pay special attention to the second paragraph) when producing this November 19, 2018 Polytechnique Montréal news release (also on EurekAlert),

A scientific breakthrough by Professor Michel Meunier of Polytechnique Montréal and his collaborators offers hope for people with glaucoma, retinitis or macular degeneration.

In January 2009, the life of 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 second) could make nanometre-sized holes appear in silicon when it was covered by gold nanoparticles. But this researcher, recognized internationally for his skills in laser and nanotechnology, decided to go a step further with what was then just a laboratory curiosity. He wondered if it was possible to go from silicon to living matter, from inorganic to organic. Could the gold nanoparticles and the femtosecond laser, this “light scalpel,” reproduce the same phenomenon with living cells?

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A very pretty image illustrating the work,

Caption: Gold nanoparticles, which act like “nanolenses,” concentrate the energy produced by the extremely short pulse of a femtosecond laser to create a nanoscale incision on the surface of the eye’s retina cells. This technology, which preserves cell integrity, can be used to effectively inject drugs or genes into specific areas of the eye, offering new hope to people with glaucoma, retinitis or macular degeneration. Credit and Copyright: Polytechnique Montréal

The news release goes on to describe the technology in more detail,

Professor Meunier started working on cells in vitro in his Polytechnique laboratory. The challenge was to make a nanometric incision in the cells’ extracellular membrane without damaging it. Using gold nanoparticles that acted as “nanolenses,” Professor Meunier realized that it was possible to concentrate the light energy coming from the laser at a wavelength of 800 nanometres. Since there is very little energy absorption by the cells at this wavelength, their integrity is preserved. Mission accomplished!

Based on this finding, Professor Meunier decided to work on cells in vivo, cells that are 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, particularly recognized for his work on the retina. “Mike”, as he goes by, is a professor in the Department of Ophthalmology at Université de Montréal and a researcher at Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Est-de-l’Île-de-Montréal. He immediately saw the potential of this new technology and everything that could be done in the eye if you could block the ripple effect that occurs following a trigger that leads to glaucoma or macular degeneration, for example, by injecting drugs, proteins or even genes.

Using a femtosecond laser to treat the eye–a highly specialized and fragile organ–is very complex, however. The eye is part of the central nervous system, and therefore 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. Mike Sapieha’s first task was therefore to ensure that a femtosecond laser could be used on one or several neurons without affecting them. This is what is referred to as “proof of concept.”

Proof of concept

Mike and Michel called on biochemistry researcher Ariel Wilson, an expert in eye structures and vision mechanisms, as well as Professor Santiago Costantino and his team from the Department of Ophthalmology at Université de Montréal and the CIUSSS de l’Est-de-l’Île-de-Montréal for their 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 the various neurons or families of neurons, such as the retina. Following the bright flash generated by the femtosecond laser, the expected phenomenon occurred: small holes appeared in the cells of the eye’s retina, making it possible to effectively inject drugs or genes in specific areas of the eye. It was another victory for Michel Meunier and his collaborators, with these conclusive results now opening the path to new treatments.

The key feature of the technology developed by the researchers from Polytechnique and CIUSSS de l’Est-de-l’Île-de-Montréal is its extreme precision. With the use of functionalized gold nanoparticles, the light scalpel makes it possible to precisely locate the family of cells where the doctor will have to intervene.

Having successfully demonstrated proof of concept, Professor Meunier and his team filed a patent application in the United States. This tremendous work was also the subject of a paper reviewed by an impressive reading committee and published in the renowned journal Nano Letters in October 2018.

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

This light scalpel is unprecedented.

Here’s a link to and a citation for the paper,

In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated Gold Nanoparticles by Ariel M. Wilson, Javier Mazzaferri, Éric Bergeron, Sergiy Patskovsky, Paule Marcoux-Valiquette, Santiago Costantino, Przemyslaw Sapieha, Michel Meunier. Nano Lett.201818116981-6988 DOI: https://doi.org/10.1021/acs.nanolett.8b02896 Publication Date: October 4, 2018  Copyright © 2018 American Chemical Society

This paper is behind a paywall.

A new class of artificial retina

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If I read the news release rightly (keep scrolling), this particular artificial retina does not require a device outside the body (e.g. specially developed eyeglasses) to capture an image to be transmitted to the implant. This new artificial retina captures the image directly.

The announcement of a new artificial retina is made in a March 13, 2017 news item on Nanowerk (Note: A link has been removed),

A team of engineers at the University of California San Diego and La Jolla-based startup Nanovision Biosciences Inc. have developed the nanotechnology and wireless electronics for a new type of retinal prosthesis that brings research a step closer to restoring the ability of neurons in the retina to respond to light. The researchers demonstrated this response to light in a rat retina interfacing with a prototype of the device in vitro.

They detail their work in a recent issue of the Journal of Neural Engineering (“Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry”). The technology could help tens of millions of people worldwide suffering from neurodegenerative diseases that affect eyesight, including macular degeneration, retinitis pigmentosa and loss of vision due to diabetes

Caption: These are primary cortical neurons cultured on the surface of an array of optoelectronic nanowires. Here a neuron is pulling the nanowires, indicating the the cell is doing well on this material. Credit: UC San Diego

A March 13, 2017 University of California at San Diego (UCSD) news release (also on EurekAlert) by Ioana Patringenaru, which originated the news item, details the new approach,

Despite tremendous advances in the development of retinal prostheses over the past two decades, the performance of devices currently on the market to help the blind regain functional vision is still severely limited–well under the acuity threshold of 20/200 that defines legal blindness.

“We want to create a new class of devices with drastically improved capabilities to help people with impaired vision,” said Gabriel A. Silva, one of the senior authors of the work and professor in bioengineering and ophthalmology at UC San Diego. Silva also is one of the original founders of Nanovision.

The new prosthesis relies on two groundbreaking technologies. One consists of arrays of silicon nanowires that simultaneously sense light and electrically stimulate the retina accordingly. The nanowires give the prosthesis higher resolution than anything achieved by other devices–closer to the dense spacing of photoreceptors in the human retina. The other breakthrough is a wireless device that can transmit power and data to the nanowires over the same wireless link at record speed and energy efficiency.

One of the main differences between the researchers’ prototype and existing retinal prostheses is that the new system does not require a vision sensor outside of the eye [emphasis mine] to capture a visual scene and then transform it into alternating signals to sequentially stimulate retinal neurons. Instead, the silicon nanowires mimic the retina’s light-sensing cones and rods to directly stimulate retinal cells. Nanowires are bundled into a grid of electrodes, directly activated by light and powered by a single wireless electrical signal. This direct and local translation of incident light into electrical stimulation makes for a much simpler–and scalable–architecture for the prosthesis.

The power provided to the nanowires from the single wireless electrical signal gives the light-activated electrodes their high sensitivity while also controlling the timing of stimulation.

“To restore functional vision, it is critical that the neural interface matches the resolution and sensitivity of the human retina,” said Gert Cauwenberghs, a professor of bioengineering at the Jacobs School of Engineering at UC San Diego and the paper’s senior author.

Wireless telemetry system

Power is delivered wirelessly, from outside the body to the implant, through an inductive powering telemetry system developed by a team led by Cauwenberghs.

The device is highly energy efficient because it minimizes energy losses in wireless power and data transmission and in the stimulation process, recycling electrostatic energy circulating within the inductive resonant tank, and between capacitance on the electrodes and the resonant tank. Up to 90 percent of the energy transmitted is actually delivered and used for stimulation, which means less RF wireless power emitting radiation in the transmission, and less heating of the surrounding tissue from dissipated power.

The telemetry system is capable of transmitting both power and data over a single pair of inductive coils, one emitting from outside the body, and another on the receiving side in the eye. The link can send and receive one bit of data for every two cycles of the 13.56 megahertz RF signal; other two-coil systems need at least 5 cycles for every bit transmitted.

Proof-of-concept test

For proof-of-concept, the researchers inserted the wirelessly powered nanowire array beneath a transgenic rat retina with rhodopsin P23H knock-in retinal degeneration. The degenerated retina interfaced in vitro with a microelectrode array for recording extracellular neural action potentials (electrical “spikes” from neural activity).

The horizontal and bipolar neurons fired action potentials preferentially when the prosthesis was exposed to a combination of light and electrical potential–and were silent when either light or electrical bias was absent, confirming the light-activated and voltage-controlled responsivity of the nanowire array.

The wireless nanowire array device is the result of a collaboration between a multidisciplinary team led by Cauwenberghs, Silva and William R. Freeman, director of the Jacobs Retina Center at UC San Diego, UC San Diego electrical engineering professor Yu-Hwa Lo and Nanovision Biosciences.

A path to clinical translation

Freeman, Silva and Scott Thorogood, have co-founded La Jolla-based Nanovision Biosciences, a partner in this study, to further develop and translate the technology into clinical use, with the goal of restoring functional vision in patients with severe retinal degeneration. Animal tests with the device are in progress, with clinical trials following.

“We have made rapid progress with the development of the world’s first nanoengineered retinal prosthesis as a result of the unique partnership we have developed with the team at UC San Diego,” said Thorogood, who is the CEO of Nanovision Biosciences.

Here’s a link to and a citation for the paper,

Towards high-resolution retinal prostheses with direct optical addressing and inductive telemetry by Sohmyung Ha, Massoud L Khraiche, Abraham Akinin, Yi Jing, Samir Damle, Yanjin Kuang, Sue Bauchner, Yu-Hwa Lo, William R Freeman, Gabriel A Silva.Journal of Neural Engineering, Volume 13, Number 5 DOI: https://doi.org/10.1088/1741-2560/13/5/056008

Published 16 August 2016 • © 2016 IOP Publishing Ltd

I’m not sure why they waited so long to make the announcement but, in any event, this paper is behind a paywall.