Ultrasonic Retinal Neuromodulation and Acoustic Retinal Prosthesis

Abstract

Ultrasound is an emerging method for non-invasive neuromodulation. Studies in the past have demonstrated that ultrasound can reversibly activate and inhibit neural activities in the brain. Recent research shows the possibility of using ultrasound ranging from 0.5 to 43 MHz in acoustic frequency to activate the retinal neurons without causing detectable damages to the cells. This review recapitulates pilot studies that explored retinal responses to the ultrasound exposure, discusses the advantages and limitations of the ultrasonic stimulation, and offers an overview of engineering perspectives in developing an acoustic retinal prosthesis. For comparison, this article also presents studies in the ultrasonic stimulation of the visual cortex. Despite that, the summarized research is still in an early stage; ultrasonic retinal stimulation appears to be a viable technology that exhibits enormous therapeutic potential for non-invasive vision restoration.

Ultrasound stimulation for non-invasive visual prostheses

“…First, the mechanism of neuromodulation of ultrasound stimulation should be more comprehensively understood. In particular, it is unclear whether the neuromodulation effect of ultrasound is universal or limited to specific cell types as well as whether the cellular compartment responding to ultrasound is existing in the degenerate retinas ( Lo et al, 2020 ). If the underlying mechanism is revealed, the ultrasound stimulation conditions (e.g., frequency, therapy duration, duty cycle, and intensity) can be further optimized to efficiently modulate neuronal activities and/or enhance spatiotemporal resolution.…”

“…Indeed, recent publications have demonstrated a CMUT array with monolithically integrated circuits can be chronically implantable even on a rat ( Seok et al, 2021a , b ). A 2D ultrasonic transducer array system would be preferred to create multi-focused patterns of activities rather than a single transducer with a raster scanning ( Lo et al, 2020 ), which requires lots of extra bulky moving components.…”

“…Permanent blindness can be caused by diverse visual diseases such as retinitis pigmentosa ( Yue et al, 2016 ), age-related macular degeneration ( Jackson et al, 2002 ), and optic neuritis ( Toosy et al, 2014 ). Although these diseases are incurable ( Lo et al, 2020 ), the implantation of visual prostheses is one of the available options for vision restoration ( Shepherd et al, 2013 ; Fernandez, 2018 ; Im and Kim, 2020 ; Kim et al, 2022 ). Recently, electrical stimulation is used for the activation of neurons in the retina, optic nerve, lateral geniculate nucleus, and visual cortex.…”

“…Ultrasound has long been used for both diagnostic imaging ( Wells, 2006 ) and therapeutic treatment ( Steiss and McCauley, 2004 ) including cancer tissue destruction ( Hsiao et al, 2016 ), proving its safety. In recent years, ultrasound stimulation technology (UST) has been used for neuromodulation of the nerve cells of the retina ( Yue et al, 2016 ; Jiang et al, 2019 ; Lo et al, 2020 ) and of the visual cortex ( Lee et al, 2016 ; Lu et al, 2021 ). The purpose of the present study is to overview recent studies regarding UST aiming for vision restoration as well as to discuss future perspectives on the development of acoustic visual prostheses.…”

Editorial for the Special Issue on Micro/Nanofabrication for Retinal Implants

“…They also compared other stimulation modalities such as ultrasonic, magnetic, and chemical stimulation, which are all at the early stage of development for retinal prosthetic application. Among those new technologies, ultrasound stimulation has been particularly outlined in the other review paper by Lo et al [7]. In the thorough review, they summarized previous representative works which acoustically stimulated not only the retina but also the visual cortex.…”