NIH-Funded Study Tests PEDF Peptide Eye Drops for Retinitis Pigmentosa and AMD

The PEDF-based eye drops significantly slowed photoreceptor loss in both animal and human-derived retinal models.

Retinal degeneration is notoriously hard to treat, especially without a needle. However, researchers at the National Institutes of Health (NIH) may have found a workaround: PEDF peptide eye drops that actually reach the retina.

The preclinical results, published in Communications Medicine, showed the potential to advance non-invasive treatment options for retinitis pigmentosa (RP) and dry age-related macular degeneration (AMD). Both conditions share a common trigger: cellular stress in the retina.^1,2 

For the first time, researchers have now shown that eye drops with pigment epithelium-derived factor (PEDF)-derived peptides can protect the retina and maintain vision cells without injections.

That’s where PEDF peptides may offer a game-changing approach.

In mouse and human models of RP, the leading peptide, H105A, preserved up to 75% of photoreceptors after just one week of treatment.

“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 in a press release from the United States’ National Institutes of Health (NIH). 

“Animals given the H105A peptide have dramatically healthier-looking retinas, with no negative side effects.”

Key findings from the PEDF peptide eye drop study

The NIH-led team conducted a study to assess two peptide formulations (17-mer and H105A), both derived from the active region of PEDF. 

Their work evaluated how well these peptides could be delivered, their safety, and their ability to protect retinal cells, using both animal models and human-derived retinal tissue.

In tests with mouse and human models of retinal degeneration, the PEDF-derived peptides—particularly H105A—showed strong neuroprotective effects. Here are the highlights:

• In mouse models of retinitis pigmentosa (RP), daily eye drops with H105A helped preserve up to 75% of photoreceptors after just one week.
  
• Mice treated with the drops showed stable vision, with healthy responses to light in ERG tests.
  
• The retina absorbed the peptides within 60 minutes, and they stayed active for up to 48 hours.
  
• In lab-grown human retinal tissue under oxidative stress, H105A stopped photoreceptor cells from dying and helped keep the structure intact.
  
• No signs of toxicity, inflammation or other negative effects were seen in any of the animal or lab tests.
  
• The drops didn’t interfere with gene therapy given afterward, indicating that the protected cells could still respond to treatment.
  
• The peptides triggered PEDF-R, which boosts phospholipase A2, an important enzyme that helps photoreceptors survive.¹

Peptide power

The research was led by Dr. Patricia Becerra and her team at the National Eye Institute (NEI), part of the NIH, working alongside colleagues from the University of Modena (Italy) and the University of Colorado’s Anschutz Medical Campus, Aurora (USA).

Building upon years of foundational work on pigment epithelium-derived factor (PEDF), the team developed smaller peptide fragments that retain their protective qualities and can reach the retina through simple eye drops.³

The results suggest a gene-independent approach that may help preserve photoreceptors in various retinal diseases and provide an interim option while gene therapies and other targeted treatments progress through development.  

The potential impact down the line is encouraging. Gene therapies for retinitis pigmentosa (RP) are progressing, but they don’t suit every patient, and access can take years. A safe, non-invasive eye drop that protects photoreceptors across different genetic mutations could offer a valuable stopgap—and perhaps a lasting solution for some.

For more information, see the NIH’s press release on the PEDF peptide eye drop study.

References

1. Bernardo-Colón A, Bighinati A, Parween S, et al. H105A peptide eye drops promote photoreceptor survival in murine and human models of retinal degeneration. Commun Med (Lond). 2025;5(1):81.
2. Gallenga CE, Lonardi M, Pacetti S, et al. Molecular Mechanisms Related to Oxidative Stress in Retinitis Pigmentosa. Antioxidants (Basel). 2021;10(6):848. 
3. Rebustini IT, Bernardo-Colón A, Nalvarte AI, Becerra SP. Delivery Systems of Retinoprotective Proteins in the Retina. Int J Mol Sci. 2021;22(10):5344.