Many of us have experienced seeing dark flecks or strings drifting in front of our eyes. Blink and these so-called “floaters” are gone. But myopia, advancing age, and diabetes can all increase the number and size of these protein clumps inside the eyeball—to the point at which they disrupt normal vision. In experiments with human eye fluid samples, researchers have found that gold nanoparticles heated with a low-energy laser can help reduce these problematic clumps (ACS Nano 2019, DOI: 10.1021/acsnano.9b04050). The technique could lead to a clinical therapy that’s superior to those currently in use.
Healthy eyeballs are filled with a transparent, jelly-like substance known as the vitreous humor that’s largely a mesh of collagen and the polysaccharide hyaluronic acid. The collagen can form insoluble globs that float within the gel, scattering light and potentially disrupting vision. Clinicians treat these problematic floaters by vitrectomy, an invasive and irreversible process that replaces the vitreous fluid with a saline solution, or by shining a high-energy laser beam into the eye to break clumps apart. Studies have found that only 38% of patients report that laser treatment helped their symptoms, and the procedure carries risks of damage to the lens or retina.
Stefaan C. De Smedt of Ghent University and his colleagues looked to gold nanoparticles for a better solution. These nanoparticles tend to remain immobile in the vitreous humor at the site of injection, but coating them with a layer of hyaluronic acid—the same molecule present in the eyeball—allows them to travel and cluster on collagen bundles. This clustering may be because the coated nanoparticles are repelled by similarly charged hyaluronic acid in the humor, allowing them to move to collagen fibers where hyaluronic acid is absent, says Félix Sauvage, a postdoctoral researcher in De Smedt’s lab and the first author on the study.
To test the coated nanoparticles, the team first heated a collagen solution, which causes the protein to clump and form fibers that mimick those in the eye. The researchers then added the nanoparticles to the solution and exposed the mixture to short pulses of low-intensity laser light. Dark-field microscopy revealed that the laser treatment broke the fibers into smaller pieces. Compared with larger nanoparticles, the 10 nm diameter gold nanoparticles they tested scattered less light, which would likely affect vision less, and required less laser energy to heat up, protecting the surrounding vitreous fluid, Sauvage says. They are also more likely to diffuse faster through the humor to reach their floater targets. “It’s a really targeted effect,” he says.
The method required about 0.1% of the energy of conventional laser therapy. “This is pretty good in terms of limiting side effects and potential damage to nearby cells,” says Michel Meunier of Polytechnique Montreal, who studies nanostructures for medicine and was not involved with the study.
In subsequent experiments, Sauvage and his colleagues found that the nanoparticle-laser treatment had no effect on the viability of cultured human Muller cells, a kind of cell found near the retina. The team also tested the technique on samples of vitreous humor taken from people who had undergone a vitrectomy and observed that floaters were smaller or broken apart after nanoparticle treatment. Studies in living organisms will be necessary to determine whether the eye can clear the nanoparticles after treatment or whether the particles cause any problems if they remain in the eye indefinitely.