Friday, June 11, 2021

The Future is in Sight: How Biology and Engineering are Solving Blindness.

Our ability to see is one of our most valuable gifts--it makes up the basis of our experience of life and everything we have come to know.  To see this gift being taken away from millions is extremely upsetting, and has inspired thousands of like-minded scientists and engineers to dedicate their lives to trying to restore sight to those who have lost it.  The challenge with blindness is, more times than not, blind people have an issue with the hardware of their vision system as compared to their software. For this reason prosthetics versus medicines have taken the lead in offering solutions for blindness. Prosthetics is an area where biology and engineering have to learn from each other immensely. The challenge is building a device that can effectively play the role of a healthy biological molecule using mechanics we trust and know how to manipulate. So far, there has been several approaches taken to tackle blindness, although none of them have come near to restoring total vision, they have given the blind some resemblance of sight which is a victory in itself. The hope is this first round of vision technologies is the proof of concept that is needed to create a truly revolutionary solution to blindness. In this article, we will discuss three different approaches to solving blindness and how they work and differ from one another. 


Artist rendering of an eye. https://www.engadget.com/researchers-combine-gene-therapy-and-event-cameras-to-partially-restore-a-blind-mans-sight-173002101.html 
                                            

How We See

The general sequence of how we see begins when light passes through our cornea, a transparent protective layer that sits on the outside of our eye and is shaped like a dome. Next, the iris, the colored part of our eye, regulates the amount of light let into the pupil. Light flows through the pupil and then through a clear barrier called the lens. This process further alters the light waves before they reach their final destination-the retina.  The retina is composed of special cells called photoreceptors, which convert these light waves to electrical signals. These signals sent out by the photoreceptors are then processed in a matrix of special cells that will eventually send a final signal up the optic nerve to the brain, where it creates what we perceive to be sight. 



Illustration showing the basic components of an eye.
https://www.nei.nih.gov/learn-about-eye-health/healthy-vision/how-eyes-work

Bionic Photoreceptors.

One of the most common reasons for blindness is having nonfunctional photoreceptors, which can be caused by genetic disorders or other diseases.  As a solution, scientists set out to design bionic photoreceptors that facilitate the role of turning light and color into electrical signals that the brain will translate to sight. The logical approach to making a technology like this work is to use a black box method in which you plug in visual inputs into a normal person and record both the electrical signal output of their photoreceptors as well as what that signal appears as when it enters the brain as an input. Combining this data and integrating it with machine learning will allow you to form a consistent algorithm that turns vision into electrical signals. A problem with this approach is that artificial photoreceptors are not exactly like real photoreceptors so applying this algorithm will not work as seamlessly as imagined. This brings the challenge to the table of trying to understand the language of electrical signals in response to light so the algorithm can be tweaked to work with artificial photoreceptors. This was described by associate scientist Dr. Daniel Rathbun at Henry Ford University as a grey box approach- a hybrid between a black and white box. Very few people have received this technology because it is still being tested but there's evidence it works.





Illustration showing how artificial photoreceptors work. https://www.youtube.com/watch?v=JyNot03-8As 


From Camera to the Brain?

The second approach completely bypasses a person's existing vision system and connects a special digital camera wirelessly to an implant in their brain. This method considers the fact that many people who are blind are lacking optic nerves or cells that transmit a signal from the retina to the brain so having a system that directly links a device to the brain is a neat solution. It is also important because we understand the nature whereby electrical signals are sent wirelessly and how the signal behaves whereas the signal through an optic nerve is less predictable. Along the same lines, having a system that we can construct that's not within the already established vision system gives us flexibility to build our own way of seeing that maybe is completely different from the method by which normal people see--but it works. In other words, building a system within another system without understanding the initial one is tough so building a separate system that can be trialed and errored until it is made to work seems like the best solution. The NIH seems to think this too as just this past year (2020) they supplied researchers at Illinois Tech pursuing this type of technology with a 2.5 million dollar grant to start clinical trials of their visual prosthesis system that goes straight from the camera to the brain.  Additionally, other designs involve using a camera that is connected to electrodes in the retina acting as essentially remote-controlled artificial photoreceptors, or in the case where someone's photoreceptors are okay but their eye structure is severely damaged, a system that displays a live feed of the camera to the their photoreceptors is a workable solution.


 Picture of a camera.  https://www.pinterest.com/chrisebullock/zed-head/


Illustration of brain. https://www.vice.com/en/article/exmynm/you-will-be-able-to-plug-your-brain-into-the-internet-456



Gene Therapy 

Gene therapy is being utilized in some cases to correct certain genetic diseases that cause photoreceptors or other parts of a person's vision system to become dysfunctional. A functional version of a gene fixed with a promoter is embedded in a safe virus that enters the vision-related cells where the gene is transcribed and translated to the correct version of the protein that was previously dysfunctional in that cell. Also, stem cells are being used to replace damaged parts of people's eyes so they can regain function of these components. For example, the cornea, the outer transparent part of your eye, has cells at the corners of it which are responsible for producing healthy cornea cells when cells have been damaged. In some cases, these stem cells can become dysfunctional and can no longer regulate the health of the cornea which leads to bad vision. What scientists can do is extract healthy cornea stem cells, grow them in a culture and put them into the diseased part of the cornea which helps restore the cornea repair system. Scientists are also experimenting with replacing faulty retinal pigment epithelial cells, which are needed for the health of the retina, with healthy ones that are derived from embryonic stem cells.


    
                                      Picture of eye with illustration of DNA strands.
 https://eye.vcu.edu/subspecialties/


The Net Method

Blindness like cancer and other complex diseases doesn't have a general solution. It not like a bacterial infection that has an antibiotic that shuts it down. Instead, each case of the disease is unique and has a different origin story by which it got to the place it is today, and thus it requires a unique treatment. So for these diseases, instead of working for one solution, we need to take multiple angles in the hope to cover the whole spectrum of variation that can occur. I like to think about solving large-scale diseases like blindness or cancer through the metaphor of a net. By creating many different tools and technologies we are creating this vast network of treatments and this net that can catch anything that comes its way. Though just like a net there are gaps between treatment methods--areas where no treatments are suitable and where things can fall through. As years go by, more nodes (treatments) are added to the net and the holes get smaller and smaller until there is always a solution to every case and nothing can get through the net.  Seeing how this problem of blindness is being attacked from so many different angles gives me hope that we are creating a life-sized algorithm to solve blindness. As in evolution, the more diversity you have the better survival you will have in a population, and in this way the more ways and approaches you take to try to solve illnesses and conditions like blindness the greatest chance you will have at solving it. 



Illustration of a network/net.
https://www.hubxygen.com/post/is-internet-set-to-become-the-biggest-energy-and-resource-consuming-machine-on-earth


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