Researchers at the National Institutes of Health (NIH) have developed promising new eye drops that significantly slow vision loss in animal models of retinitis pigmentosa, offering hope for patients with various degenerative retinal diseases.
The innovative treatment contains small peptide fragments derived from pigment epithelium-derived factor (PEDF), a naturally occurring protein in the eye that helps preserve retinal cells. These findings, published in Communications Medicine, represent a potential breakthrough for treating inherited retinal diseases that currently have limited therapeutic options.
"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 age-related macular degeneration," said Patricia Becerra, Ph.D., chief of NIH's Section on Protein Structure and Function at the National Eye Institute and senior author of the study.
The Science Behind the Treatment
All degenerative retinal diseases share a common feature: cellular stress. Though the sources of stress vary—with dozens of mutations and gene variants linked to retinitis pigmentosa, AMD, and other disorders—high levels of cellular stress ultimately cause retinal cells to lose function and die. This progressive loss of photoreceptor cells leads to vision loss and eventually blindness.
Previous research from Becerra's laboratory had demonstrated that the natural protein PEDF could help retinal cells resist cellular stress. However, the complete PEDF protein is too large to penetrate eye tissues and reach the retina effectively. Additionally, the complete protein has multiple functions in retinal tissue, making it impractical as a treatment.
To overcome these limitations, the research team developed two peptide formulations:
- "17-mer," containing 17 amino acids found in the active region of PEDF
- H105A, a similar peptide that binds more strongly to the PEDF receptor
"For the first time, we show that eye drops containing these short peptides can pass into the eye and have a therapeutic effect on the retina," said Alexandra Bernardo-Colón, the study's first author.
Impressive Results in Animal Models
When administered once daily to young mice with retinitis pigmentosa-like disease, the H105A peptide demonstrated remarkable efficacy in slowing photoreceptor degeneration and vision loss. The researchers used specially bred mice that typically lose the majority of their photoreceptors within a week after cell loss begins.
The results were striking:
- Mice receiving the peptide eye drops retained up to 75% of photoreceptors
- Treated mice maintained strong retinal responses to light
- Control mice receiving placebo had few remaining photoreceptors and little functional vision
Importantly, peptides applied as drops on the eye's surface reached high concentration in the retina within 60 minutes and gradually decreased over the next 24 to 48 hours. Neither peptide caused toxicity or other side effects.
Bridging to Gene Therapy
While various gene-specific therapies are under development for many types of retinitis pigmentosa, these PEDF-derived peptide eye drops could play a crucial role in preserving cells while patients wait for gene therapies to become clinically available.
To test this potential complementary approach, collaborators Valeria Marigo, Ph.D. and Andrea Bighinati, Ph.D., from the University of Modena, Italy, treated mice with gene therapy at the end of the week-long eye drop regimen. The results were encouraging—the gene therapy successfully preserved vision for at least an additional six months.
Human Potential
To assess whether the eye drops could work in humans without direct human testing, the researchers collaborated with Natalia Vergara, Ph.D., from the University of Colorado Anschutz. They tested the peptides in a human retinal tissue model of retinal degeneration grown from human cells.
When exposed to chemicals inducing high levels of cellular stress, the human retinal tissues without peptide treatment died quickly. However, tissues treated with the peptides remained viable, providing crucial preliminary evidence supporting potential human trials.
"Given these results, we're excited to begin trials of these eye drops in people," said Becerra.
Clinical Implications
Retinitis pigmentosa affects approximately 1 in 4,000 people worldwide, causing progressive vision loss that often begins in childhood or young adulthood. The condition currently has no cure, and treatment options are limited.
These PEDF-derived peptide eye drops represent a potential breakthrough in treatment approach for several reasons:
- They target a common mechanism (cellular stress) underlying multiple retinal diseases
- The eye drop formulation offers a non-invasive delivery method
- The treatment preserved significant retinal function in animal models
- No toxicity or side effects were observed
The research was funded by the NEI Intramural Research Program, with additional support from the Prevention of Blindness Society, Fondazione Telethon, HEAL-ITALIA Foundation, CellSight Development Fund, and Research to Prevent Blindness.
As the research moves toward human clinical trials, these eye drops could potentially offer a new therapeutic option for patients with retinitis pigmentosa and other degenerative retinal diseases, helping to preserve vision while more targeted gene therapies continue development.
