UT Arlington researchers are exploring a better method for initiating certain gene therapies that could better fight the sight-deteriorating disease retinitis pigmentosa. This research is funded by the National Institutes of Health.
Dr Samarendra Mohanty, Assistant Professor of Physics, at UT Arlington, is focused on using near-infrared ultrafast laser beam to deliver genes that allow expression of light-sensitive proteins, called opsins, into specific cells. That proteins’ expression allows researchers to influence neural activity through optical or light stimulation – a technique known as optogenetics.
In the past, the genes have been delivered to cells by virus. That method can have drawbacks, such as immune responses, in addition to the benefits. In Mohanty’s method, a laser beam creates a transient sub-micrometer size hole, which allows for the gene encoding the proteins to permeate through the cell membrane. It can limit the risk of immune response, as well as delivering larger genes than viral methods, he said.
The scientists claim that with the minimally invasive near-infrared method, DNA and other impermeable molecules can be effectively delivered only to the places most required. In retinitis pigmentosa, the peripheral retina begins to lose light sensitivity due to loss of photoreceptors. With this method, a laser can deliver the genes only to the required part of the retina, making those neurons respond to light again. This method will be more effective than a virus, where the genes are delivered everywhere, potentially causing complications in areas that are already working fine.
Optogenetic stimulation also holds promise for influencing neurons in the brain. Scientists, including Mohanty’s research group, are researching ways it could be used to understand how the brain works or to intervene in case of neurological disorders or to affect behavior.
Ultimately, Mohanty’s team has a goal of creating all optical, or light-based, control and monitoring of cell activity. So, in addition to the light-assisted delivery of genes, the researchers also will work on refining methods for stimulating the neural activity using near-infrared and visible light. Some of those methods are described in a recently published paper called “Fiber-optic two-photon optogenetic stimulation,” which appeared in the journal Optics Letters.
Mohanty’s lab at UT Arlington also will use a method called phase-sensitive interferometry, to monitor the changes in neurons that result from the activation by light. The interferometry method is called “label-free” because unlike fluorescence, it uses the change in behavior of light rays, rather than staining, to track changes at the sub-nanometer level.
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