A team of scientists at the National Institutes of Health (NIH) has developed an eye drop that successfully slowed vision loss in mice with an inherited eye disease.
In mice both with retinitis pigmentosa (RP) and lab-grown human retina tissue with damage akin to age-related macular degeneration (AMD), a daily drop prevented photoreceptors in the eye from degrading by delivering a shortened version of a protective protein called pigment epithelium-derived factor (PEDF).
Compared to mice given placebo, treated mice had longer and thicker regions of photoreceptor tissue and had eyes more responsive to light, the authors reported in Communications Medicine on March 21.
Untreated mice eventually saw their photoreceptors and vision degrade due to RP, with them having almost no vision left after a week.
“While not a cure, this study shows that PEDF-based eye drops can slow progression of a variety of degenerative retinal diseases in animals, including various types of retinitis pigmentosa and dry AMD,” S. Patricia Becerra, Ph.D., a chief scientist at the NIH’s National Eye Institute and senior author of the study, said in a March 21 release. “Given these results, we’re excited to begin trials of these eye drops in people.”
Becerra and her team had previously found that the loss of PEDF in the retina, which occurs naturally with aging, is connected with retinal damage and conditions like AMD. But because the protein is so big, getting it into the retina—which sits at the back of the eye—to prevent that damage without an injection is tricky.
To get around this problem, the researchers isolated two regions of the PEDF protein that they knew from previous work to be involved in its protective function. They turned those regions into standalone proteins, called 17-mer and H105A, that are smaller than PEDF and able to nimbly navigate to the back of the eye to reach the retina. H105A is a variant of 17-mer.
The team tested two versions of the eye drops, one with 17-mer and another with H105A, and found both protected mice with RP from vision loss.
To further probe H105A’s effectiveness, the researchers grew human retina tissue into organoids in the lab. They then exposed the organoids to extract from cigarette smoke, which is known to cause damage similar to AMD. Treating the organoids with H105A prevented the retina cells from succumbing to the smoky stress.
The organoid results “provide proof-of-concept for the efficacy of the H105A peptide in preventing damage to human retinal cells, further supporting its translational potential for retinal degenerative diseases,” the authors wrote.
With the eye drops showing signs of success, the team next tried a different delivery approach: gene therapy. After a week of eye drops, the team injected a functional copy of a gene that codes for the H105A protein into the eyes of mice with RP. The gene treatment protected the rodents’ vision for an additional six months, according to the release.
Gene therapies are a promising approach for RP, the authors said in the release, because many forms of the disease begin in childhood and progress over time. If approved for humans, the new eye drops could help preserve vision until gene therapies become available, the authors wrote.
Many treatments for eye diseases require injections into the eye itself; for example, Regeneron’s blockbuster drug Eylea (aflibercept), which is approved for a suite of eye diseases, typically needs to be injected once every month or two for wet AMD.
In contrast, “eye drop administration is simpler, less invasive, and poses lower risk of retinal damage, which could improve patient compliance,” the researchers wrote in their paper.