Lan Yue, PhD: Will Nanophotoswitches One Day Restore Sight to the Blind?

In the ever-present quest to restore sight to the blind, a new contender has emerged: iridium pyridine-based nanophotoswitches.

Lan Yue

Lan Yue, PhD

Nanophotoswitches could help improve visual signal transduction in cases where deteriorated photoreceptors fail to transmit visual signals to the retina ganglion cells, according to Lan Yue, PhD, one of the researchers at USC’s Roski Eye Institute who’s spearheading trials on the technology. In previous studies, Yue and colleagues demonstrated that nanophotoswitches elicit responses to light when injected into the eyes of rats.

It’s still too early to say whether they could do the same in humans, but according to Yue, nanophotoswitches hold one important advantage: they have the potential to help patients achieve very high acuity prosthetic vision compared to currently available treatments.

In a recent follow up study presented at the 2018 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO), data suggested that nanophotoswitches may act on multiple components of the retinal neural circuitry that could suppress its direct action on retinal ganglion cells via synaptic transmission. When administered intravitreally, the nanophotoswitch molecules remained stable and active in the ocular environment “up to at least one day post injection,” researchers wrote.

Yue sat with MD Magazine at Hawaii Convention Center to elucidate the work she’s doing, and what the future might hold.

Lan Yue, PhD:

At ARVO this year, I’m going to present our research on nanophotoswitches, which are a family of molecules that respond to light. We hope that it can be used towards building a molecule-based retinal prosthesis to restore sight to the blind.

We have tested the activity of these molecules with advanced electrophysiological technologies at USC, and we also imaged the fluorescence of these molecules with our multiphoton system at USC too.

In photoreceptor degenerated eyes, the inner retina—namely, the ganglion cells—lost their signal input from the deteriorated photoreceptors, and therefore the visual signal transduction in the retina is lost. Our tech aims to bypass the damaged photoreceptors and directly activate the retinal ganglion cells so when those molecules are injected into the eye, they will diffuse retinal cells in the membrane of the retinal ganglion cells. Under visible light exposure, those molecules will be excited, and either donate or accept electrons from other molecules in the environment. When they accept the electrons they will change the membrane potential of the ganglion cells, thereby inducing spiking activity of the cell types.

The advantage of this technology is that since the acting unit is single molecule, it has the potential to achieve very high resolution, very high acuity prosthetic vision compared to what you see in the market now. In the market, you see electronic metal prostheses that have restored some level of vison to the blind, but the resolution is typically pretty poor. Using our technology, we hope to find a way to establish high resolution prosthetic vision in these patients.

We cannot give out a timeframe at this moment, but were working really hard towards translating the technology from bench to the clinic. Right now there are a couple of questions that need to be answered. First, how long these molecules can stay stable and active in the ocular environment. To understand this we need to study the removal mechanism of these molecules in the eye. Second, whether we can develop an improved or optimized delivery technology to target these molecules to specific retinal neurons, such that the neuronal signals of these ganglion cells can better incorporate into the visual signal pathway.

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