An organic retinal implant designed in Italy can stimulate retinal neurons and send signals to the brain, restoring near-normal vision indefinitely to rats with degenerative blindness without causing apparent damage to the rats’ eyes. That’s the claim of the researchers who developed it, who believe it could potentially lead to treatments for a major cause of blindness in humans. Other researchers, however, are more cautious.
Retinitis pigmentosa describes multiple genetic disorders that cause the photoreceptors on the retina to die. These lead to blindness, even though the other neurons concerned with signal processing and the optic nerve remain functional. There is currently no effective clinical treatment for the condition, but several groups are developing various proposals to effectively replace these lost photoreceptors by stimulating the retinal neurons artificially. While this could one day restore a patient’s vision, these approaches face severe difficulties. For example, most of the implants require a power supply, and wiring into the eyeball is extremely tricky. One solution is a photovoltaic cell that generates a voltage using only the incoming light, but this faces two principal problems. First, previous researchers have found the intensity of ambient light insufficient to stimulate the neurons. Secondly, silicon is much stiffer than nervous tissue: “In the long term, [silicon] can induce a reaction by the tissue,” says neuroscientist Fabio Benfenati of the Center for Synaptic Neuroscience and Technology in Genoa, “leading to encapsulation, [scarring] and things like that.”
In the new research, materials scientist Guglielmo Lanzani of the Center for Nano Science and Technology in Milan and colleagues designed a more flexible, organic retinal implant based on a polymer solar cell. They deposited a thin layer of conductive polymer onto a silk-based substrate and covered it with a semiconducting polymer. When the semiconductor absorbs a photon, it creates an electron–hole pair called an exciton. The positive holes are drawn into the conducting polymer, whereas the electrons remain in the semiconductor, causing a negative charge.
Surgeons led by ophthalmologist Grazia Pertile of Sacro Cuore Hospital near Verona implanted the devices underneath the retinas of Royal College of Surgeons (RCS) rats – a strain of rats that reliably develop retinitis pigmentosa owing to a genetic mutation also found in some human cases of the disease. They placed the implants such that the semiconducting polymer was in contact with the retinal neurons, so absorption of light would apply a negative voltage to the cells. After 30 days, when the swelling from the surgery had completely subsided, Benfenati’s group compared the rats’ vision with both untreated RCS rats and healthy rats.
They first tested the pupil’s contraction in response to light, finding that although it was significantly impaired in untreated RCS rats, it was near normal in rats with the implant. In further tests using an electrode in the primary visual cortex, the researchers showed that implanted rats’ light sensitivity and visual acuity was substantially better than that of untreated RCS rats, and positron emission tomography showed that the metabolism of their primary visual cortices was higher. Furthermore, the rats – which naturally prefer dark environments – avoided light more effectively.
The researchers tested the rats again later, both after 180 days and after 300 days: they found that, although the quality of the implanted rats’ vision declined, it stayed just as good relative to the other rats. “There is a generalized decrease in [the rats’] sight with age,” explains Benfenati. The recovery of the rats’ vision appears greater than can be explained by simple photovoltaics, so the researchers suspect other effects are involved, although precisely what these are remains unclear.
After dissecting the rats, the researchers tested prostheses removed from their eyes and showed that they worked similarly to prostheses stored in sterile conditions. The researchers are now testing an adapted implant in pig’s eyes: “We believe, based on these data, we could probably attempt the first [human] implant…within the next two years,” says Benfenati.
“The article is indeed interesting,” says ophthalmologist Mark Humayun of the University of Southern California in Los Angeles. He is impressed by the simplicity of using light to stimulate the implant, although he cautions: “The RCS rat retina is known to be much easier to stimulate. When it comes to a patient with longstanding retinal degeneration, we have found that ambient light intensity is insufficient and it requires intensified light – often multiple Suns.”
Daniel Palanker of Stanford University, is more sceptical, noting that “their RCS rats responded to every visual test, indicating that they still have photoreceptors”. He also pointed out that sub-retinal surgery is known to help preserve photoreceptors in RCS rats, and therefore these rats have better vision. He noted that, in their test of the implant, the researchers used light six million times more intense than the light levels to which the rats responded. “This indicates that the visual response has nothing to do with the photovoltaic response of the polymer,” he concludes. The researchers attempt to rule out this explanation by showing that a silk implant without the photovoltaic coating does not work, but Palanker is unconvinced: “The difference between the photovoltaic polymer and the passive control could be due to electrochemical reactions, which might help preserve photoreceptors better,” he says. “I’m not sure, but given other major problems, it’s not the central issue here.”
The research is described in Nature Materials.