Activity of Retinal Neurons Can Be Modulated by Tunable Near-Infrared Nanoparticle Sensors

Abstract

The vision of patients rendered blind by photoreceptor degeneration can be partially restored by exogenous stimulation of surviving retinal ganglion cells (RGCs). Whereas conventional electrical stimulation techniques have failed to produce naturalistic visual percepts, nanoparticle-based optical sensors have recently received increasing attention as a means to artificially stimulate the RGCs. In particular, nanoparticle-enhanced infrared neural modulation (NINM) is a plasmonically mediated photothermal neuromodulation technique that has a demonstrated capacity for both stimulation and inhibition, which is essential for the differential modulation of ON-type and OFF-type RGCs. Gold nanorods provide tunable absorption through the near-infrared wavelength window, which reduces interference with any residual vision. Therefore, NINM may be uniquely well-suited to retinal prosthesis applications but, to our knowledge, has not previously been demonstrated in RGCs. In the present study, NINM laser pulses of 100 μs, 500 μs and 200 ms were applied to RGCs in explanted rat retinae, with single-cell responses recorded via patch-clamping. The shorter laser pulses evoked robust RGC stimulation by capacitive current generation, while the long laser pulses are capable of inhibiting spontaneous action potentials by thermal block. Importantly, an implicit bias toward OFF-type inhibition is observed, which may have important implications for the feasibility of future high-acuity retinal prosthesis design based on nanoparticle sensors.

Nanoparticle-based optical interfaces for retinal neuromodulation: a review

“…Similarly, the optimal performance specifications of a nanoparticle-based retinal interface – in terms of spatial and temporal resolution, response dynamics and exposure to long and repeated stimulation – cannot be confidently specified at this stage. While the recent results reported for photothermal stimulation and inhibition of RGCs by gold nanoparticles ( Begeng et al, 2023 ) suggest that a high degree of spatial and temporal control is theoretically possible, there will almost certainly be tradeoffs, for example in terms of heat buildup during repeated stimulation. Moreover, further investigation is required to establish whether RGCs become desensitized to repetitive stimulation via nanoparticle interfaces, as has been observed for electrical stimulation with conventional retinal prostheses ( Jensen and Rizzo, 2007 ; Freeman and Fried, 2011 ; Soto-Breceda et al, 2018 ).…”

“…Nanoparticle-mediated retinal protheses offer an opportunity to selectively activate ON and OFF RGCs by targeting nanoparticles to different cell types. Some progress in this direction has been made by Begeng et al (2023) , where it has been shown that OFF RGCs can be preferentially inhibited using gold nanorods and long near-infrared pulses. The mechanism of inhibition during nanoparticle-enhanced infrared neuromodulation is due to the phenomenon known as thermal block, mediated by voltage-gated potassium channels suppressing action potentials at elevated temperatures ( Ganguly et al, 2019 ).…”

“…These results suggest that NINM has potential to be a safe alternative to existing retinal prosthesis technologies, although the strategy of targeting nanoparticles to photoreceptors may be not suited for late-stage retinal degeneration, which corresponds to the atrophy of rods and cones (see Section 2). As a generalization of this approach, our lab has subsequently demonstrated that NINM can be applied directly to RGCs in explanted rat retinae, without the need for genetic modification ( Begeng et al, 2023 ). We found that shorter (sub-millisecond) laser pulses evoked robust RGC stimulation by capacitive current generation, while longer 200 ms laser pulses were capable of inhibiting spontaneous action potentials by thermal block.…”

“…With that exception, the less invasive techniques discussed in Section 3 may offer advantages in terms of suppressing spontaneous RGC activity. The successful demonstration of safe thermal block with NINM in RGCs by Begeng et al (2023) shows promise for the development of nanoparticle-based retinal interfaces that combine stimulatory and inhibitory inputs to achieve a high visual acuity. However, by requiring exogenous nanoparticle absorbers, NINM forgoes a key advantage of conventional INM.…”

A tissue-engineered neural interface with photothermal functionality

“…Due to the oxidation process used to fabricate GO, the recombination of electron-hole pairs present in its basal area confers photothermal properties to the bulk material. 92,93 Nonetheless, the scaffolds containing only GO require a higher irradiance to evoke depolarization when compared to the scaffolds containing GO and AuNRs.…”