Ultrasound stimulation for non-invasive visual prostheses

Abstract

Globally, it is estimated there are more than 2.2 billion visually impaired people. Visual diseases such as retinitis pigmentosa, age-related macular degeneration, glaucoma, and optic neuritis can cause irreversible profound vision loss. Many groups have investigated different approaches such as microelectronic prostheses, optogenetics, stem cell therapy, and gene therapy to restore vision. However, these methods have some limitations such as invasive implantation surgery and unknown long-term risk of genetic manipulation. In addition to the safety of ultrasound as a medical imaging modality, ultrasound stimulation can be a viable non-invasive alternative approach for the sight restoration because of its ability to non-invasively control neuronal activities. Indeed, recent studies have demonstrated ultrasound stimulation can successfully modulate retinal/brain neuronal activities without causing any damage to the nerve cells. Superior penetration depth and high spatial resolution of focused ultrasound can open a new avenue in neuromodulation researches. This review summarizes the latest research results about neural responses to ultrasound stimulation. Also, this work provides an overview of technical viewpoints in the future design of a miniaturized ultrasound transducer for a non-invasive acoustic visual prosthesis for non-surgical and painless restoration of vision.

Keywords: artificial vision; neuromodulation; ultrasound stimulation; vision restoration; visual prosthesis.

FIGURE 1

Schematics showing the ultrasound stimulation mechanism and ultrasound stimulation methods. (A) Physical mechanisms of ultrasound-based excitation on neurons. Biophysical effects of ultrasound such as (1) Temperature rise, (2) Bubble formation and cavitation, and (3) Mechanical force. Adapted from Yoo et al. (2022). (B) Microbubble-assisted ultrasound stimulation of mechanosensitive channels. Adapted from Rivnay et al. (2017). (C) Piezoelectric nanoparticle-assisted ultrasound stimulation of voltage-sensitive ion channel. Adapted from Rivnay et al. (2017).

FIGURE 2

Focused ultrasound treatment for visual restoration. (A) Retinal neurons were excited by ultrasound waves which lead to the generation of the neural signal. These signals are transmitted to the brain via the optic nerve and the brain activity is recorded from the visual cortex or the superior colliculus. Adapted from Qian et al. (2022). (B) The circular racing array device for ultrasonic stimulation. Adapted from Yu et al. (2019). (C) In simulated acoustic intensity profiles, the acoustic focus was effectively projected to the targeted stimulatory site localized in the calcarine fissure (a), and acoustic energy was delivered to the visual cortex (b). Adapted from Lee et al. (2016).