NIH researchers develop reduced eyesight in animals

Researchers at the National Institutes of Health (NIH) have developed eye drops that extend the vision of an animal model of hereditary diseases that lead to progressive loss of vision in humans called retinitis pigmentitis. Eye drops contain a small fragment of proteins derived from humans and found in the eyes, called pigment epithelial-derived factor (PEDF). PEDF helps preserve cells in the eye’s retina. The report of the study was published in Communication Medicine.

“While it is incurable, this study shows that PEDF-based eye drops can slow the progression of a variety of degenerative retinal diseases in animals, including various types of retinitis pigmentosa and age-related macular degeneration (AMD),” said Dr. Patricia Becerra of NIH. “Given these results, we are excited to start trials of eye decline in these people.”

All degenerative retinal diseases share common cellular stress. While the source of stress may vary – mutations and genetic mutations are associated with retinitis pigmentosa, AMD and other diseases – high levels of cell stress can cause the gradual loss of function and death of retinal cells. Progressive loss of photoreceptor cells leads to loss of vision and ultimate blindness.

Previous studies in Becerra’s lab showed that in mouse models, the natural protein PEDF can help retinal cells avoid the effects of cellular stress. However, the full pEDF protein is too large to reach the retina through external eye tissue, and the intact protein has multiple functions in the retinal tissue, making it impractical as a treatment. To optimize the molecules’ ability to preserve retinal cells and help them reach the eye, Becerra developed a series of short peptides derived from the PEDF region that support cell viability. These small peptides can move through eye tissue and bind to the PEDF receptor protein on the surface of the retina.

In the new study, led by first author Alexandra Bernardo-Colón, Becerra’s team created two eye drop formulas, each containing a short peptide. The first peptide candidate called “17-mer” contains 17 amino acids found in the active region of PEDF. The second peptide, H105A, is similar, but is stronger than that of the PEDF receptor. The droplets on the surface of the eye were found in the retina within 60 minutes, and a high concentration was found in the retina, slowly decreasing over the next 24 to 48 hours. Peptides cause neither toxicity nor other side effects.

H105A was taken once a day to young mice with retinitis, and H105a slowed down photoreceptor degeneration and vision loss. To test the drops, the researchers used special breeding mice that lost their photoreceptors shortly after birth. Once cell loss begins, most photoreceptors die within a week. When given a weekly period of peptide eyes, mice retained 75% of the photoreceptors and continued to respond strongly to the retinal response of light, while mice given placebo had little remaining photoreceptors this weekend and had little functional vision.

“This is the first time we have shown that eye drops containing these short peptides can enter the eyes and have a therapeutic effect on the retina,” said Bernardo-Colón. “Given that animals with H105a peptide have a significantly healthy retina, there is no negative impact.”

Various gene-specific therapies are being developed in many types of retinitis pigmentosa, which often begin with progress in childhood and over the years. These PEDF-derived peptide eye drops may play a crucial role in preserving cells while waiting for these gene therapies to be available clinically.

To test whether photoreceptors preserved by eye drop treatment are sufficient to make gene therapy work, collaborator Dr. Valeria Marigo, Ph.D. Dr. Andrea Bigiginati of the University of Modena, Italy, treated mice with gene therapy at the end of a week-long eye instillation protocol. The gene therapy successfully retained vision for at least six months.

To see if eye drops can play a role in humans – the researchers worked with Dr. Natalia Vergara of Aurora at the University of Colorado Anschutz University to test peptides in a human retinal tissue model for retinal degeneration. Retino-like tissue grows in human cells and is exposed to chemicals that induce high levels of cellular stress. Without peptides, cells in the tissue model die rapidly, but because of the peptides, retinal tissue remains alive. These human tissue data provide a key first step in human trials that support eye drops.

The study was funded by the NEI Intramural Research Program. The Society for Prevention of Blindness, Contezine TV, Heal-Italia Foundation, Cellight Development Fund, and research on Prevention of Blindness provide additional funding.

References: Bernardo-Colón A, Bighinati A, Pareew Heaces S, Debnath S, Piano I, Adani E, Corsi F, Corsi F, Gargini C, Vergara N, Marigo V and Marigo V and Becerra sp. “H105a peptide eye drops promote photoreceptor survival in mouse and human models of retinal degeneration.” March 21, 2025, Comms Med.