PURPOSE: Acoustic retinal prosthesis has been put forward using high-frequency US with non-invasive and high-resolution advantages. But its application is limited by the difficulties in fabrication, energy consumption and acoustic attenuation. In the present study, low-frequency focused ultrasound stimulation (LFUS) had been demonstrated to activate retinal ganglion cells (RGCs) in rat retinas. The neurophysiological properties of RGC responses to LFUS were also investigated.
METHODS: A 2.25 MHz focused ultrasound transducer (D=0.75 in., SF=2.0 in.) was used to stimulate the rat retina which was cultured in a multi-electrode array system (MEA2100, MCS , Fig. 1). The acoustic property was evaluated by hydrophone (UMS3, Precision acoustics). Ultrasound (US) stimulation was modulated at pulsed mode. Light stimulation was modulated in the same mode to give an uniform field flashes. The electrophysiological data collected from MEA was detected for neural spikes and sorted by Plexon Offline Sorter. Only channels recording single-cell activities were adopted for subsequent analysis. Peri-stimulus time histograms and raster plots were plotted for each RGC using Spike 2.
RESULTS: In total, 116 retinal ganglion cells (RGCs) from 7 retinas were sorted and classified into four types according to light responses. The firing activity of 114 RGCs were modulated by repeated US stimulation. This suggested that low-frequency focused ultrasound stimulation (LFUS) could activate RGCs. The US responses didn’t correspond to the standard light responses and varied greatly between cell types. Besides, dual-peak responses to US stimulation were observed which were not reported previously. The temporal response properties of RGCs, including latency, firing rate, and response type, could be modulated by changing acoustic intensity.
CONCLUSIONS: These findings might imply a temporal neuromodulation effect of LFUS and provided an important foundation for the development of acoustic retinal prosthesis.