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N. Farah, S. Matar, A. Marom, L. Golan, S. Shoham; Photo-Absorber Based Neural Stimulation for an Optical Retinal Prosthesis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):3470.
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Retinal prostheses for patients with outer-retinal degenerative diseases could interface directly with surviving retinal neurons using electrode array implants. Direct optical stimulation using light-gated ion channels, has recently been introduced as an alternative method for cell-type specific, minimally-intrusive control of neurons. However, optogenetic methods are based on viral trasnfection (or the generation of transgenic animals), which may pose significant hurdles prior to their clinical application. Here, we introduce and characterize a new physical method for neural excitation that could be used in an optical retinal prosthesis without requiring transfection. The new method is based on distributing physical photo-absorbers, and directing focused laser beams on the absorbers to induce thermal transients.
We dispersed micron-scale carbon particles in several acute and cultured neuronal preparations, including a retina preparation where they were dispersed next to the ganglion cells. To induce thermal transients, a focused laser beam (several microns in diameter) was directed onto the particles and pulsed for periods lasting between 100 microseconds to 10 milliseconds. To characterize the properties of the induced thermal transients, experiments using the temperature sensitive dye RU were performed and complemented by theoretical analysis. The resulting neural activity was recorded using fluorescent calcium sensitive dyes imaging (OGB-AM and Fluo-4-AM).
Focused illumination pulses absorbed by the carbon-based photo-absorbers, led to rapid (milliseconds timescale) thermal transients with a well-defined and highly-localized dynamics which was visualized using temperature-sensitive dyes, and matched theoretical predictions. Using calcium sensitive dye imaging, we observed that the thermal transients repeatedly excited neurons in the close vicinity of the absorbers, when the pulse power exceeded a certain threshold.
photo-absorber induced neural-thermal stimulation (PAINTS) introduced here is capable of repeatedly stimulating neurons in a highly specific manner in both space and time. Because it is physical, and can potentially interface with a diverse set of display devices, photo-absorbers and different laser wavelengths, it has properties that make it a powerful technology towards the development of optical retinal neuro-prosthetics.
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