Minimally-Invasive, High-Resolution Restoration of Vision Using Photothermal Activation of Retinal Neurons

Abstract

Purpose : Retinal prosthesis aims to restore vision by implanting electronic hardware in irreversible photoreceptor degeneration diseases. The limitations of current clinical devices are that the visual acuity is still worse than legal blindness and requires complex implant surgery. To break the limitations, we utilized intravitreal injectable retinal ganglion cells (RGCs)-binding gold nanorods (AuNRs) as miniature near-infrared (NIR) laser enhancers to photothermally activate RGCs and thereby restore vision with negligible side effects.

Methods : By intravitreally injecting Thy-1 antibody-conjugated gold nanorods (AuNRs) in mice and stimulating RGCs with a square pattern of NIR laser beams (980 nm wavelength), we recorded neural activities of RGCs on live retinal explants of GCaMP3 mice via fluorescence Ca²⁺ imaging. We examined how AuNRs-enhanced NIR stimulation interfaces with RGCs on temperature-sensitive ion channels via applying multiple transient receptor potential vanilloid (TRPV) blockers. To validate the efficacy in vivo, we recorded electrocorticograms from the visual cortex of mice injected with either AuNRs or PBS while illuminating the square pattern of NIR laser on the retina.

Results : Compared to PBS-injected retinas (n = 4), NIR laser projection evoked increases in the Ca²⁺ fluorescence of the AuNRs injected retinal neurons in a laser intensity-dependent manner, up to 5 % △F/F (n = 9). The change of fluorescence for all the responsive RGCs was highly localized inside the 100 μm-width square pattern of the NIR laser-illuminated area, indicating a spatial resolution of 100 μm. RGCs responses were blocked by TRPV1 antagonist rather than TRPV4 antagonist, suggesting this photothermal approach transiently opened TRPV1 channel on the neural membrane to activate RGCs via surface plasmon resonance. For in vivo, with the 160-μm (3 degrees field-of-view) square pattern of NIR laser projection, AuNRs injected mice (n = 6) elicited significant evoked potentials on the visual cortex in a laser intensity-dependent manner, but PBS-injected mice (n = 4) did not respond to NIR light.

Conclusions : Our study provides the promising potential for the development of a novel generation of a minimally-invasive, high-resolution photothermal retinal prosthetic device without genetic manipulation to restore vision in blindness.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.