Microelectrode device with photoreceptor-like cells from stem cells activates the retina naturally and maintains ON/OFF selectivity – new hope for AMD and RP patients.
Are we on the way to a world without blindness? New biomedical developments point to a future where implants will replace photoreceptors that degenerate with age.
Vision is the most important sense for humans, and about 90 percent of the information we acquire comes from the sense of sight,” explains Prof. Yossi Mendel, head of the Laboratory for Vision Science and Engineering at Bar-Ilan University. “It is not without reason that many expressions link vision to wisdom and understanding, for example, ‘How wise is he who sees the future.’ For people who are blind from birth, we currently have no solution. Their brains develop differently, so even if their vision is corrected later on, they still will not be able to see. Even a problem like cataracts, which can be solved today with simple surgery, must be solved in early childhood – otherwise the patient will remain blind even without the cataract. But technology can help people who saw in the past and whose photoreceptors have degenerated over the years.”
The retina is located at the back of the eye and is responsible for receiving the image and converting it into neural information, which is transmitted to the brain via the optic nerve. The retina consists of over a hundred types of nerve cells, and a total of hundreds of millions of cells, which allow it to receive images even in extremely low lighting and contrast conditions.
Along with these extraordinary abilities, the complexity of the eye and retina also carries with it vulnerability to various diseases that cause blindness.
In the Western world, which enjoys a long life expectancy, the most common cause of blindness is age-related macular degeneration (AMD). Alongside this degeneration, which is mainly common among the elderly, there is an entire family of genetic diseases called retinitis pigmentosa (RP) that cause retinal degeneration. In both AMD and RP, the photoreceptors are damaged, but the other layers of the retina remain relatively normal. Therefore, researchers around the world are trying different methods to replace the photoreceptors. One method is an “artificial retina” – replacing the biological photoreceptors with technological photoreceptors, which aim to electrically stimulate the next cells in the visual chain, thereby restoring the sight of millions.
“Our retina consists of three main layers,” explains Prof. Mendel. “The first layer is the photoreceptors that absorb light. This is followed by a layer of bipolar cells that receive the information from the photoreceptors and process it. The bipolar cells transmit the information to ganglion cells that digitize the information, turn it into pulses (sort of like bits, similar to a computer), and send it to the brain, to the visual cortex – where it naturally undergoes additional information processing. The artificial retinal implant that we are building is a light-receiving device that electrically activates cells similar to photoreceptors, which transmit the information to the next layer, which is biological – and from there the process continues just like in normal vision.”
The device that Prof. Mandel and his team are developing, with the help of a research grant from the National Science Foundation, consists of electrodes located at the bottom of tiny wells, each of which is ten microns (one hundredth of a millimeter) in size. In addition, inside each well is a cell similar to a photoreceptor, which was created in the laboratory by differentiating human stem cells. After the implant is implanted, the cells in the wells send out extensions and connect to the next layer in the patient's retina - the bipolar cells. When light hits the device, an electric current is created in the electrodes, and the electric current activates the cells in the wells. These cells, in turn, activate the patient's retina naturally by secreting substances that are used for communication between nerve cells - neurotransmitters.
We are trying to imitate the visual system, which many years of evolution have brought to its amazing capabilities.
“There are currently artificial retinas that are already being tested on humans, and the results so far are relatively poor,” says Prof. Mandel. “Although there are some promising directions for improving these results, there are a number of limitations that prevent us from achieving vision close to our natural vision, both in terms of visual acuity and in other aspects such as contrast sensitivity. To deal with these limitations, we built the electrodes with a structure of small bars, which allows us to isolate the electric field, so that one electrode does not activate the cells next to it. This is very important, because the resolution achieved today with an artificial retina is about 20 times less good than natural, normal vision. You can read – but you need very large letters. Among other things, this poor resolution stems from the spread of the electric field. Using the bars, we direct the stimulation and thus achieve a much higher resolution using much less electricity – and this also has clear practical advantages.”
Another reason for the poor quality of vision currently obtained from artificial devices is that existing artificial retinas directly activate the cells in the retina using electrical pulses, and not in the way that is natural to the retina, that is, using the substances used for interneuronal communication - the neurotransmitters.
We are trying to imitate the visual system, which many years of evolution have brought to its amazing capabilities. To do this, we add cells at the bottom of the retina as necessary intermediaries between the photoreceptors and the bipolar cells. Furthermore, activation via neurotransmitters allows us to activate certain cells and not others in the retina, just as the healthy eye knows how to use different visual pathways. For example, if we read black text on a white background, we view it using a pathway called OFF. Whereas white text on a black background is read using a neural pathway called ON. The different pathways have important roles in the visual system. The fact that our artificial retina allows us to preserve this selectivity of the eye is of great significance.”
“We still have a long way to go before our device is implanted in people,” concludes Prof. Mandel, “but this path is interesting and full of fascinating challenges that many researchers in the laboratory are working on: Dr. Nayrouz Farah, Dr. Amos Marcus, doctoral student Gal Shafon, Dr. Yoav Shmol, Erel Lesnoy, doctoral student Tamar Azard Leibowitz, Picara Panthon and Prof. Zeev Zalevsky.”
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Fascinating, I was very interested!
I would very much like to meet this professor.
That will also help me see again.