The objective of the proposed research is to develop a novel neurophotonic molecular switch for light-activation of neurons. A visual prosthesis based on this nanophotoswitch (NPS) has the potential to improve the visual acuity for the millions of patients suffering from retinal degenerative diseases, such as retinitis pigmentosa and age-related macular degeneration. This proposal is very innovative. The biophysical mechanism is completely differentiated from electrical devices and other molecular photo-switch-based approaches. Beyond vision restoration, it is a generally useful approach for controlling excitable cells. If successful, it may have a great impact on patients who are underserved by current treatments.
The interdisciplinary research provides excellent educational opportunities for participating graduate and undergraduate students. The proposing team has an exceptional record on inclusion of women, under-represented minorities, and undergraduates in their research. They also have a good track record on outreach to the local community, and planned outreach activities include Research Experience for Teachers and activities for K-12 students.
Nanophotoswitch (NPS) offers a new tool to elicit electrical activity for basic science studies of neuronal function, both in vitro and also potentially in vivo. The hypothesis is based on the NPS design and results of pilot experiments, that light induces an electrical dipole in the NPS. Preliminary data indicate that an NPS based on ruthenium bipyridine (Rubpy) inserts into cell membranes and upon visible-wavelength illumination triggers action potentials in cultured excitable cells and in wholemount rat retina. When injected into the eye of blind photoceptor-degenerate rats, visual stimulation induces electrical activity in the superior colliculus. It was also demonstrated that NPS can both depolarize or hyperpolarize the membrane, depending on the environmental redox potential. This unique combination of bi-directional modulation of the membrane potential in one biophotonic switch affords the ability to both activate and inhibit the action potential firing of the illuminated cells with the same molecule, presenting largely increased flexibility in neuronal control. The NPS would be useful in studying any electrically excitable cell, including, for example, cardiomyocytes, smooth muscle cells, neuroendocrine cells, and certain glial and cancer cells. Since light-activated signaling unit is individual neurons, a visual prosthesis based on NPS system has the potential to provide higher visual acuity for the millions of patients with photoreceptor loss due to retinal degenerative diseases, such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Distinct from other nano-scale optical cellular modulating approaches using optogenetics or azobenzene-based photoswitches, this approach obviates the need for gene manipulation, toxic ultraviolet illumination or immunogenic molecules, due to the unique light-to-electrical signal transduction mechanism of the NPS.
