Towards a Noninvasive Retinal Prosthesis: In vivo Ultrasonic Retinal Stimulation

Retinal degenerative diseases, the principal causes of human blindness, are caused by the degeneration of retinal photoreceptors while the remaining cells in the retinal pathways are left mostly intact. Since the retina is an accessible CNS structure, it presents a favorable target for low intensity ultrasonic stimulation, which could potentially bypass the degenerated photoreceptors and restore a visual signal via the remaining retinal neurons. Moreover, this signal can be spatially patterned using ultrasound arrays and holographic algorithms. Previously, characterization studies of visual evoked potentials and electrical responses from isolated retinas demonstrated that ultrasonic stimulation is a promising option for stimulating retinal activity. However, direct measurements of the response to non-invasive ultrasonic stimulation of the retina in vivo are still missing.

Here, we examine the effects of US on mouse retinas in vivo for vision restoration using acoustic neuro-stimulation. A fluorescent calcium indicator of neural activity was introduced into mouse retinas and fluorescence changes were recorded upon application of US. The effect of the various pulse parameters on successful stimulation was investigated and compared. The observed responses included both stimulation and suppressive neural responses to the US stimuli, whose spatial distributions was largely separable. The responses also showed a systematic increase in peak change in fluorescence as the US pressure increased and as the PRF increased. Our results demonstrate the ability to modulate retinal activity in vivo and motivate future research that will explore and refine the stimulation protocols and parameters.