Gold nanorods help blind mice see

Plasmonic nanoparticles—tiny rods, spheres, or shells made of gold, silver, or other metal—are exceptionally good at converting light to heat. That capacity has many potential biomedical uses. For example, if targeted to a malignant tumor and zapped with a laser, nanoparticles can help cook the tumor to death without harming the surrounding tissue.

Now Dasha Nelidova and her colleagues are working on a new application that couples nanoparticles’ heat to an existing sensory system. The researchers, at the Institute of Molecular and Clinical Ophthalmology in Basel, Switzerland, are combining plasmonic nanoparticles and gene therapy to develop a treatment for some forms of blindness.

From the cornea to the optic nerve, any part of the visual system can malfunction; correspondingly, blindness can take many forms. Among the most common in the developed world is age-related macular degeneration, in which the retina’s light-sensitive cells gradually die off. There are ways to slow the disease’s progression, but no treatment can yet restore the vision already lost. Nelidova and colleagues hope to fill that gap.

The researchers were inspired by some species of snakes, such as pit vipers, that have specialized facial organs equipped with heat-sensitive proteins. Those snakes can “see” in the IR to detect the body heat of prey and predators even in the dark. Researchers can endow retinal cells in other species with the same thermoresponsiveness by loading the gene for the protein into a benign virus and injecting it into the eye—cells take up the gene, start expressing the protein (shown in blue in the figure), and embed it into their own cell membranes.

But the proteins by themselves aren’t sensitive enough to rival normal vision. That’s where the nanoparticles come in. Delivered to the eye along with the gene-bearing viruses, the nanoparticles (shown in gold) absorb light and convey concentrated heat to the thermoresponsive proteins. The researchers tethered the nanoparticles to the proteins by decorating them with antibodies (black) that bind to a tag on the protein (red).

Nelidova and colleagues used rod-shaped nanoparticles tuned to absorb at 915 nm, a near-IR wavelength that humans can’t normally see. That wavelength choice ensures that the new nanoparticle-mediated vision doesn’t interfere with any remaining healthy photoreceptors.

So far, the researchers have performed their procedure on lab mice and on donated postmortem human retinas. The results are promising. The treated mice, formerly blind, could see well enough to learn a behavioral response to a flash of near-IR light. (D. Nelidova et al., Science 368, 1108, 2020 .)