Look and learn: two-photon microscopy
Researchers at Johns Hopkins University School of Medicine have used photonics to find out more about how learning and memory-building take place in the brain.
Using in vivo two-photon microscopy, a fluorescence imaging technique that allows imaging of living tissue up to 1mm thick, they were able to measure levels of AMPAR molecules which help send messages between neurons in mouse brains. A fluorescent DNA-encoding version of these molecules was injected into mouse brains and an electrical pulse used to force the neurons to absorb the AMPAR DNA. Researchers were then able to measure the levels of fluorescence coming from the tagged AMPARS – higher amounts of florescence indicated increased AMPAR activity, a sign that learning and memory-building was occurring.
A 20% increase in AMPAR activity was observed in the motor cortex, part of the brain that controls and moves muscles, when the mice were learning how to reach for a food pellet with their paws. The same 20% increase was also seen in the visual cortex, which makes sense when considering how important vision is for motor control. When the experiment was repeated in the dark, this AMPAR increase dropped to 10%, indicating that the mice used different sensory cues to learn the task.
Specialised light-activated modulators were then used to shut down neurons in the mice’s visual cortex. Mice trained to reach for the pellets in the light were unable to complete the task with their visual cortex shut down, but the mice trained to grab the pellet in the dark were still able to do so.
The research indicates that motor-based learning occurs across the entire brain, rather than solely in the motor cortex as previously believed.
Rabbits with retinopathy: LED contact lenses
South Korean researchers at the Pohang University of Science and Technology (POSTech) have developed light-emitting diode (LED) contact lenses to aid in the diagnosis of diabetes and the treatment of diabetic retinopathy. In its final form, the device is planned to use near-infrared light to analyse glucose concentration in tears and deliver drugs to treat retinopathy accordingly.
So far the technology has been trialled in rabbits with diabetic retinopathy. The research team was able to place the LED contact lenses in the rabbits’ eyes and have them irradiate light repeatedly for a month. After this time they found there was a significant reduction of angiogenesis, the formation of new vessels cells from pre-existing ones, in the rabbits’ retinas.
Angiogenesis is a key driver of diabetic retinopathy, indicating that the devices could well be clinically feasible. The POSTECH team was also able to develop a Bluetooth system that could allow patients to check their diabetic diagnosis results on their phones.
Preliminary clinical tests for the developers are expected to be done in the first half of 2020.
Resource-limited record keeping: quantum dots
People’s vaccine histories could one day be recorded under their skin using quantum dots.
Engineers at Massachusetts Institute of Technology have developed a microneedle platform that selectively delivers microparticles into the skin. The microparticles contain quantum dots, which store the person’s vaccination history in a pattern of dye that is delivered under the skin at the same time as the vaccine. The particles are invisible to the naked eye, but can be detected using infrared light via a smartphone.
The copper-based dots emit near-infrared light. Around four nanometres in diameter, they are encapsulated in biocompatible microparticles of 20 nanometres in diameter, which remain in place under the skin after being injected.
The microneedle patch can be customised to imprint different patterns in accordance with the different type of vaccine being delivered. Only one and a half millimetres long, they partially dissolve under the skin and release their contents within two minutes.
The technology could be a boon to healthcare providers in resource-limited settings, where medical record keeping is poor. The quantum dot patterns were visible in cadaver skin after up to five years of simulated sun exposure and could be detected nine months after vaccine administration in rats. Mixing the vaccine with the dye did not affect the efficacy of the vaccine.
The research team are now assessing how best to implement the technology. They’re also working towards expanding the amount of data that can be encoded into a single pattern and assessing the overall safety of the miniature devices.
Mice and microglia: light stimulation to treat dementia
Neurodegenerative diseases are often rooted in dysfunction of the neuroimmune system, so it’s thought that manipulating this could have significant therapeutic potential. The number of deaths due to Alzheimer’s and other forms of dementia is predicted to rise by 41% between 2015 and 2030, making the fight against them one of the most pressing in modern medicine.
Studies have found that exposure to light pulsing at 40 Hz triggers gamma frequency neural activity in the brains of mice, prompting the release of a surge of microglia. Microglia are the brain’s primary immune cells, indicating that pulsing light is in some way able to manipulate the neuroimmune system. Microglia are responsible for purging amyloid beta plaque, the junk protein that accumulates between the brain cells of Alzheimer’s patients.
Researchers at the Georgia Institute of Technology have exposed human subjects to similar stimulation. They have designed a visor, which flickers 40 Hz light into the eyes while the subject wears earphones that play a 40 Hz sound.
The flicker was seen to lead to a surge in the expressions of cytokines in subjects’ brains, which are known to promote microglial phagocytic states. It also rapidly changed the phosphorylation of proteins in the NF-κB and MAPK pathways, which are known to regulate cytokines. These surges began within about 15 minutes of exposure to the flickering.
The results indicate that some sort of rapid immune response is triggered by 40 Hz visual stimulation, which could have applications in the treatment of neurodegenerative conditions.
Random flicker, constant light and 20 Hz flicker each induced their own unique cytokine expressions. The research team has advised that patients to not attempt to improvise their own light therapies at home.
Tumour imaging technology: OTL38 in the operating room
A multi-institution study featuring six universities and clinics across the US has developed a near-infrared light imaging technique called OTL38 to enhance the visualisation of lung cancer tissue in the operating room.
OTL38 is composed of a near-infrared dye and a targeting molecule, which attaches itself to folic acid based receptors on cancer cells. During surgery, an endoscope can be used to guide surgeons around the lung to identify exactly where malignant tissue has grown.
The technique could help surgeons improve the quality of lung cancer operations by making it easier to identify hard-to-find pieces of tumour tissue. As well as finding previously undetected cancers while a patient is under the knife, it could help them better assess if an entire tumour has been removed or if cancerous cells have been left behind.
In a phase two clinical trial, OTL38 was found to improve outcomes for 26% of the patients who took part in the trial. Phase three trials are now underway.