Could eye drops treat retinal disease in the future?
Researchers have developed PEDF-based eye drops that show promise in slowing retinal degeneration in mice with retinitis pigmentosa, potentially offering a non-invasive treatment option for preserving vision in the future.
A collaboration of American and Italian researchers has developed eye drops that have shown encouraging effects in slowing the rate of retinal degeneration in mouse models of retinitis pigmentosa (RP).
The drops contain a small section of a larger, naturally-occurring protein called pigment epithelium-derived factor (PEDF), which is known to have protective effects on photoreceptors, the light-sensitive retinal cells that deteriorate in RP. Importantly, PEDF’s ability to impede photoreceptor death is independent of the underlying genetic cause of the degeneration, suggesting that PEDF-based treatments could be applicable to a large proportion of those living with inherited retinal conditions, regardless of which gene is causing their sight loss.
The research team, led by Alexandra Bernardo-Colón at the National Eye Institute in the US, was mindful of the fact that many of the treatments currently in development for inherited retinal conditions involve invasive methods of administration, including injection into the back of the retina and into the jelly of the eyeball. They were therefore keen to explore much easier routes to the retina, including the use of eye drops.
However, the full length PEDF protein is too large to pass through the outer eye tissues to reach the retina, so the researchers chopped it up into smaller pieces, focusing on sections that are most active in inducing protective mechanisms. When these protein fragments, or peptides, were applied in drops to the surface of the mouse eye, they were found at high concentrations in the retina within about an hour, before levels then fell away over the next day or two.
When administered once daily to young mice with RP-like disease, the drops slowed photoreceptor degeneration and vision loss. The investigators used specially bred mice that lose their photoreceptors shortly after birth. Once cell loss begins, the majority of photoreceptors die in a week. When given peptide eye drops through that one-week period, mice retained up to 75% of photoreceptors and continued to have strong retinal responses to light, while those given a placebo had few remaining photoreceptors and little functional vision at the end of the week.
There are of course significant differences between the mouse and human eye, not least in terms of size, so there will be a lot more testing to do to see if these eye drops have the potential to work in human disease.
The researchers did also test the PEDF peptides’ ability to protect human photoreceptors from cellular stress, by applying them directly to mini retinas grown in the lab from stem cells. Again, the results were encouraging, and will help build a picture of whether this treatment approach might be viable in the future for those living with RP. The research team have stressed that it will not provide a cure, but could slow deterioration, and might even be used alongside other treatments.
Full paper at H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration | Communications Medicine .