PEDF Eye Drops Slow Vision Loss in RP Models

A team at the National Eye Institute (NEI), part of the NIH, has developed and tested eye drops containing fragments of pigment epithelium-derived factor (PEDF)—a naturally occurring protein in the eye—to delay retinal degeneration in animal models. The results, published in Communications Medicine, show potential for a novel treatment pathway for retinitis pigmentosa (RP), dry age-related macular degeneration (AMD), and related diseases.

"While not a cure, this study shows that PEDF-based eye drops can slow progression of a variety of degenerative retinal diseases in animals," said Dr. Patricia Becerra, senior author of the study and chief of NEI's Section on Protein Structure and Function. “Given these results, we're excited to begin trials of these eye drops in people.”

Targeting Retinal Cell Stress with Small Peptides

Degenerative retinal diseases like RP and AMD share a common underlying feature: chronic cellular stress that leads to photoreceptor death and eventual blindness. PEDF is known for its protective role in the retina, but the full-length protein is too large and multifunctional to be therapeutically practical via eye drops.

To overcome this, Becerra’s team designed small peptide fragments that retain PEDF's neuroprotective activity and can reach the back of the eye. Two candidate peptides were tested:

• 17-mer: A 17-amino-acid segment from the active region of PEDF

• H105A: A modified version with enhanced receptor binding

Both peptides successfully penetrated eye tissues and reached the retina without inducing toxicity. H105A, in particular, showed potent effects in preserving retinal structure and function when administered daily in young mice models of RP.

Preserving Vision and Enhancing Gene Therapy Readiness

The treatment helped retain up to 75% of photoreceptors and maintained light responsiveness compared to placebo-treated mice. These results are particularly encouraging as they suggest PEDF peptide drops can prolong the therapeutic window for gene therapy interventions.

In collaboration with Italian researchers, the team tested gene therapy on mice following one week of peptide treatment. The results demonstrated preserved vision for at least six months, indicating that retinal cells maintained by peptide drops remained functional and receptive to further therapy.

Human Retinal Tissue Models Show Comparable Protective Effect

Although human trials have not yet begun, the research team collaborated with the University of Colorado Anschutz to test the peptides on human-derived retinal tissue models. Under chemically induced stress, untreated tissue deteriorated rapidly, while peptide-treated samples remained viable.

These promising results support the translational potential of PEDF peptide-based drops as a non-invasive treatment approach for inherited retinal diseases.

Conclusion

The development of PEDF-derived peptide eye drops by NIH scientists marks a significant step toward accessible therapies for retinitis pigmentosa and similar conditions. While human trials are pending, the strong efficacy in both animal models and human tissue analogs offers hope for a future non-invasive, broad-use retinal therapy.

Reference:

Bernardo-Colón, A. et al. H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration. Communications Medicine (2025). DOI: 10.1038/s43856-025-00789-8