# Plasmonic Retinal Prosthesis

> **NIH NIH R01** · BROWN UNIVERSITY · 2020 · $398,481

## Abstract

SUMMARY
Among various approaches to restore vision, including optogenetic stimulation and stem cell therapy, only the
electrode-based retinal prosthesis has validated its clinical promises. However, it suffers from fundamental
limitations: it requires a complicated surgery for device implantation, has both the limited number and fixed
location of stimulation sites, and above all, has a low spatial resolution since electric currents spread in
conductive media like the retina. A decade ago, photothermal stimulation with infrared light opened the possibility
of ‘remotely’ activating neurons without the aid of optogenetics, but the strong water absorption of infrared light
leads to bulk tissue heating and associated adverse effects. To enable cellular-resolution, ‘remote’ neural
activation without the bulk heating, we have demonstrated that a combined use of gold nanoparticles and near-
infrared light (negligibly absorbed by water) can produce highly-localized heat via surface plasmon resonance,
and this can activate neurons by generating capacitive membrane currents and/or opening temperature-sensitive
ion channels. We also have shown that appropriate chemical conjugation of nanoparticles further enhances the
efficacy of near-infrared stimulation. This promising neuromodulation approach, however, has yet not
demonstrated its potential as a retinal prosthesis. Here, we propose to develop, optimize, and validate this novel
technology, termed plasmonic retinal prosthesis, and compose its potential with several important advantages
when compared to the electrode-based retinal prostheses: (1) it does not require any device implantation but
only involves intravitreal injection of gold nanorods (AuNRs); (2) the single-cell resolution can be achieved in
vivo; (3) stimulation locations or targeted ganglion cells are freely adjustable; (4) the number of activatable
neurons per unit time can be as high as 100,000 neurons per second (in our pilot setup); and (5) the performance
is further upgradable after ‘installation’ as the relevant technologies advance because every key component
locates outside the eye. We will develop this promising technology through theoretical study, ex vivo optimization,
in vivo validation, and long-term testing. First, since it is essential in any novel neural interface to have an
accurate model of the system in order to optimize the design, we will advance our mathematical neuron model
to investigate two mechanisms currently under debate and determine the initial parameters for the following
animal experiments (Aim 1). Next, using our custom experimental setup that integrates a scanning laser system
and fluorescence microscope, we will develop and optimize single-cell stimulation of retinal ganglion neurons in
retina explants of mice with genetically-encoded Ca2+ indicators, followed by both the demonstration of patterned
multi-neuron stimulation and the optimization of AuNR chemistry (Aim 2). Finally, we will integrate our
experime...

## Key facts

- **NIH application ID:** 9999603
- **Project number:** 5R01EY030569-02
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Jonghwan Lee
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $398,481
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999603

## Citation

> US National Institutes of Health, RePORTER application 9999603, Plasmonic Retinal Prosthesis (5R01EY030569-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9999603. Licensed CC0.

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