6 FUTURISTIC FIXES THAT COULD HELP THE BLIND SEE AGAIN

Vision Quest: Futuristic Fixes That Could Help the Blind See Again
By Greg Miller, Wired, 11 March 2013.

Last month the U.S. Food and Drug Administration for the first time approved a device capable of restoring sight to the blind. The Argus II (named after the 100-eyed giant of Greek mythology) uses a small electrode array surgically implanted in the eye to stimulate neurons in the retina. It's a far cry from restoring 20-20 vision, but the device allows users to see areas of high contrast, such as curbs and crosswalks. That's a huge deal for people trying to live more independent lives.

As remarkable as this is, it's just the beginning. Scientists are working on innovative new ways to restore sight to the blind using tools borrowed from materials science, chemistry, genetic engineering, and stem-cell biology. In this gallery we take a look at six strategies that in the not-so-distant future could make blindness a thing of the past.

1. Argus II

Image via The New York Times

The first and only retinal implant approved for human use, the Argus II was developed over nearly 25 years by biomedical engineer and ophthalmologist Mark Humayun of the University of Southern California. A tiny camera in a pair of goggles worn by the user transmits the visual scene to a small video-processing unit worn on the belt. The processor sends signals back up to the goggles, which beam them wirelessly to the retinal implant. The implant's 60 electrodes stimulate neurons in the retina in a pattern that roughly matches the visual scene.

The current version enables a blind user to recognize a doorway, follow a sidewalk, or find a dropped set of keys, Humayun says. The next step will be a software upgrade that adds digital zoom capabilities to allow users to see nearby objects better. With 8x zoom, Humayun says, plates and silverware at the dinner table would become recognizable and wearers could begin to read large text.

2. Alpha IMS

Several other groups are working on retinal implants similar to the Argus II. The Alpha IMS, developed by German researchers, has light-sensitive photodiodes built into the implant itself, making goggles unnecessary. It also uses 1,500 electrodes, compared to 60 for Argus II, which in principle should improve the resolution of what patients see.

So far 36 patients have received Alpha IMS implants in clinical trials. In a study published last month in Proceedings of the Royal Society B, researchers studied nine of these patients and found that most had experienced real-life improvements in their ability to see. Two men who met their wives after they'd lost their sight were able to make out features of their faces for the first time, says clinical ophthalmologist Katarina Štingl of the University of Tübingen, who led the study. The implant enabled patients to recognize household objects like telephones, doorknobs and sinks, and at meals they could distinguish light-coloured noodles from dark-coloured beef and - just as important - red wine from white.

3. Photovoltaic arrays

One engineering challenge for implants like the Argus II and Alpha IMS is the need to power the electrodes inside the eye. Both systems have wires coming out the the implant that make it bulkier and more tricky for surgeons to install. At Stanford University, physicist Daniel Palanker is working on an alternative: electrode arrays powered by light itself.

His group has developed flexible silicon arrays packed with tiny photovoltaic elements that convert light to electric current, much like the photovoltaic cells inside solar panels do. Because the arrays require no wires, they are easy to implant and can be tiled to cover the retina with thousands of electrodes. In experiments with rats, Palanker and colleagues recently demonstrated that the arrays provide enough current to fire neurons in the retina.

But ambient light alone wouldn't be bright enough to power the arrays for a human user, so Palanker's team is developing goggles that increase the amount of light reaching the implants. The goggles shift incoming light to the normally invisible infrared range. That shift is necessary, Palanker explains, because many legally blind people still have some functioning photoreceptors, so simply amplifying visible light could produce painfully bright spots.

4. Optogenetics

Image: Inna Reutsky-Gefen and Shy Shoham/Nature Communications

In a healthy eye, photoreceptor cells called rods and cones convert light into electrochemical signals that propagate through a network of other neurons in the retina, and ultimately on to the brain. These other neurons aren't sensitive to light, so when the rods and cones are ravaged by disease, blindness is the inevitable result. Or maybe not. Recently developed genetic-engineering tools have allowed scientists to bestow new light-sensing talents on neurons that aren't normally able to detect light.

Most of these tricks involve genes from algae and other microorganisms that encode light-sensitive proteins. Scientists have restored sight to blind rats and mice by injecting their eyes with viruses that stick these genes into neurons. Treated animals can tell light from dark and detect motion, but it's hard to know exactly how well the rodents can see, says neuroscientist Volker Busskamp of Harvard University.

These optogenetic methods don't require any fancy electronics or complicated surgery, and a single injection into the eye could potentially restore vision for several years. It might even be possible one day to restore colour vision by inserting genes for proteins sensitive to different wavelengths of light, Busskamp says. That would be extremely difficult with any of the other strategies.

5. Photoswitch compounds

Why use gene therapy to make neurons sensitive to light when a simple drug could accomplish the same thing? That's what Richard Kramer and his colleagues at the University of California, Berkeley, are trying to do.

Last year in Neuron they described a "photoswitch compound" called AAQ that has two key features: It bends in response to light, and it latches onto ion channels, the proteins that make neurons electrically active. When Kramer and colleagues treated retinas from congenitally blind mice with AAQ, retinal neurons began firing in response to light. And when they injected the compound into the mice's eyes (after anesthetizing them, of course), the animals avoided bright places, as the nocturnal rodents normally tend to do. The effects lasted less than 24 hours, though.

More recently, Kramer's team has been working on a new photoswitch compound that looks even more promising. Compared to AAQ it's 100 times more sensitive to light, he says, and lasts for several days.

6. Stem cells

Several common forms of blindness result from the death of the light-sensitive rods and cones in the retina. To replace these cells, or at least slow their loss, scientists are turning to stem cells and their remarkable ability to morph into a variety of different cell types.

Several groups are investigating stem-cell therapies aimed at replenishing a retinal pigment epithelium cells, which surround the rods and cones and help keep them alive. The biotech company Advanced Cell Technology, for example, has a clinical trial underway for people with macular degeneration, a common cause of vision loss in the elderly, using replacement cells created from human embryonic stem cells as a treatment.

Researchers in Japan hope to get started soon on a clinical trial for macular degeneration using stem cells created by reprogramming cells taken from the patients' skin. This would be a landmark trial for the entire field of stem-cell research because it would be the first-ever human trial with so-called iPS cells, or induced pluripotent stem cells. These cells, which earned the scientists who first created them a Nobel Prize last year, have the advantage of coming from the patient instead of a donor, thereby avoiding the threat of rejection by the patient's immune system and sidestepping the ethical baggage associated with embryonic stem cells.

These trials are more preventive than restorative, says Dennis Clegg, a stem-cell researcher at the University of California, Santa Barbara. The next big leap would be stem-cell therapies that replace rods and cones after they've died off, he says. But there are several hurdles, not least of which is getting newly created photoreceptors to properly insert themselves into the existing neural circuitry in the retina. "There have been a couple promising reports, but there's still a ways to go," Clegg said.

Top image: Argus II. Image credit: Mark Humayun/USC.

[Source: Wired. Edited. Some images added.]