Experiments in nanotechnology labs have been successful in potential ophthalmic applications such as using nanoparticles to create scaffolding that can repair damaged tissue and subsequently restore vision, as well as to produce instantaneous hemostasis in eye injuries.
New Orleans-Nanomedicine, a branch of nanotechnology, could have various applications in ophthalmology because of its potential to design living structures to solve mechanical problems. Successful experiments in nanobiotechnology labs already have shown promise in ophthalmic applications such as tissue repair and subsequent vision restoration, development of contrast enhancement agents, and as a means to stop bleeding in the eye during surgery, said Rutledge Ellis-Behnke, PhD, in a presentation here at the American Academy of Ophthalmology annual meeting.
"Most of my work is in how to reconnect disconnected parts of the brain," said Dr. Ellis-Behnke, a researcher in the Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology (MIT), Cambridge, and associate professor in the Department of Anatomy, Li Ka Shing Faculty of Medicine, University of Hong Kong. "I use behavior as the assay or the readout to determine whether we were successful."
In the most basic terms, Dr. Ellis-Behnke's work involves building structures with molecules. Describing a few of the investigations being pursued in his labs at MIT and at the University of Hong Kong, he discussed in vivo experiments on regeneration of the optic nerve using a self-assembled peptide nanofiber scaffold.
"If we could create an environment that was permissive for axon growth in young animals, the axons should be able to regrow through that," he said.
Collaborating with investigators from Hong Kong, Dr. Ellis-Behnke first tested the technique in hamsters that were just a few days old. The optic nerve tract was severed to mimic traumatic brain injury and deprive the animals of vision. Investigators then injected either saline or scaffolding material into the cut. In a process called "nano neuro knitting," the scaffolding allowed the axons to regenerate. Sight was restored as the nano particles wove themselves into a nanofiber that bridged the gap between the severed nerves.
Because this result was not surprising in young animals, the experiment was replicated in adult hamsters. In the older hamsters, however, the investigators made the cut in the superior colliculus in a way that also removed all visually guided orienting behavior. As with the young hamsters, the tissue knitted itself back together.
Almost all of the animals completely recovered following treatment; their progress was followed through several months of behavioral testing that was videotaped and painstakingly reviewed. Surgical error was at fault in the two animals that did not recover functional vision, Dr. Ellis-Behnke said.
This technology is not ready for testing in humans, he added, but results of the animal experiments are promising for repairing tissue and preventing or treating eye diseases. Dr. Ellis-Behnke said that he has performed additional studies with combination treatments that achieved better return of function and better reinnervation.
In related work, Dr. Ellis-Behnke and colleagues have experimented with nano-contrast-enhancement agents that would enable them to see axons regrowing in blind eyes as this growth occurs. Following a cycle of injections of manganese chloride, surgeries, and treatment, they were able to observe a 12% to 15% rate of regeneration in the superior colliculus despite damage to more than 80% of the retina. The investigators now are working with less-damaging contrast enhancement agents.
"The upshot of all this is that you actually can look at axons regrowing in live animals," he said. "Where we're trying to go with this is to determine whether we can we do that in humans."
He and his team also have used contrast enhancement agents to study diffusion rates in the optic nerve of glaucomatous eyes. One technique they have tested is diffusion tensor imaging, which could reveal whether an eye has myelin disruption or death, a precursor to retinal ganglion cell death in some forms of glaucoma.
Immediate hemostasis using self-assembling peptides is another application of nanomedicine, Dr. Ellis-Behnke said. The material constructs a nanofiber barrier that achieves complete hemostasis within seconds when applied directly to a wound or tissue. "We're not impacting the clotting cascade, and we're not affecting the immune system by using this," he said.
In the eye, an injection of the nanoparticles could stop a bleeding cut inflicted during surgery in about 15 seconds, Dr. Ellis-Behnke said, adding that a follow-up to the original paper on this technique and its long-term outcomes will be published soon.
The material is made from amino acids and is nontoxic. More than 95% of it typically is broken down by the body and is excreted in the urine, and the remainder is used to build scaffolding. It has been used in more than 1,000 laboratory animals so far and does not appear to cause any additional damage, he said.
Broader applications of nanotechnology could affect all medical specialties, Dr. Ellis-Behnke said. For example, it could help with targeted delivery of medication as well as preservation. Nanomaterials could be thought of as specialized "packing peanuts" that form a structure around the medication while it is being broken down or help preserve it, he said.
Nanotechnology also could have a substantial effect on the targeting of medication as well as on pharmaceutical manufacturing and delivery, he said.
Dr. Ellis-Behnke closed his presentation with an analogy between nanotechnology and building the pyramids of ancient Egypt.
"The Egyptians were going through the same issues we're going through right now. They were using new math, new materials, and new transport techniques to build structures of the size that they had no idea what the limitations were going to be," he said.
"We're exactly the opposite of that. We're trying to build new structures with new materials and new mathematics and trying to handle things far smaller than we can see-and in some cases comprehend-and build structures that we don't completely understand the ramifications of. But I think it's very, very exciting to be in this field," Dr. Ellis-Behnke concluded.OT