NIH researchers develop eye drops that slow vision loss in animals

Press release

Friday, March 21, 2025

A treatment shows potential to slow the progression of human degenerative eye diseases, including retinitis pigmentosa.

PEDF protein model alongside the 17-mer and H105A peptides. Amino acid 105, which is changed from histidine in PEDF and the 17-mer peptide to alanine in H105A, is shown in green. Image credit: NEI. Alt tag: 3D image of a PEDF protein model.NEI

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Researchers at the National Institutes of Health (NIH) have developed eye drops that prolong vision in animal models of a group of inherited diseases that cause progressive vision loss in humans, known as retinitis pigmentosa. The eye drops contain a small fragment derived from a protein made by the body and found in the eye, known as pigment epithelium-derived factor (PEDF). PEDF helps preserve retinal cells. A report on the study is published in Communications Medicine.

"Although not a cure, this study shows that PEDF eye drops can slow the progression of various degenerative retinal diseases in animals, including various types of retinitis pigmentosa and dry age-related macular degeneration (AMD)," said Patricia Becerra, Ph.D., section chief on the structure and function of proteins of the NIH at the National Eye Institute and lead author of the study. “Given these results, we are excited to begin human trials of these eye drops.”

All degenerative retinal diseases share cellular stress. Although the source of this stress can vary (dozens of genetic mutations and variants have been linked to retinitis pigmentosa, AMD, and other disorders), high levels of cellular stress lead to progressive loss of function and death of retinal cells. The progressive loss of photoreceptor cells leads to vision loss and, eventually, blindness.

Previous research from Becerra's lab found that, in a mouse model, the naturally occurring protein PEDF may help retinal cells resist the effects of cellular stress. However, the full-length PEDF protein is too large to pass through the outer tissues of the eye and reach the retina, and the full-length protein has multiple functions in retinal tissue, making it impractical as a treatment. To optimize the molecule's ability to preserve retinal cells and help it reach the back of the eye, Becerra developed a series short peptides derived from a region of PEDF which promotes cell viability. These small peptides can cross ocular tissues to bind to PEDF receptor proteins on the surface of the retina.

In this new study, led by first author Alexandra Bernardo-Colón, Becerra's team created two eye drop formulations, each containing a short peptide. The first candidate peptide, called a "17-mer," contains 17 amino acids found in the active region of PEDF. A second peptide, H105A, is similar but binds more strongly to the PEDF receptor. Peptides applied to mice as drops on the surface of the eye were detected in high concentrations in the retina within 60 minutes, then slowly declined over the next 24 to 48 hours. Neither peptide caused toxicity or other side effects.

When administered once daily to young mice with a disease like retinitis pigmentosa, H105A slowed photoreceptor degeneration and vision loss. To test the drops, the researchers used specially bred mice that lose their photoreceptors shortly after birth. Once cell loss begins, the majority of photoreceptors die within a week. After administering peptide eye drops during this one-week period, the mice retained up to 75 % of their photoreceptors and continued to exhibit a strong retinal response to light, while those given a placebo had few remaining photoreceptors and limited functional vision at the end of the week.

"For the first time, we demonstrate that eye drops containing these short peptides can penetrate the eye and have a therapeutic effect on the retina," said Bernardo-Colón. "Animals given the H105A peptide have significantly healthier-looking retinas, with no negative side effects."

Various specific gene therapies are being developed for many types of retinitis pigmentosa, which typically begin in childhood and progress over many years. These PEDF-derived peptide eye drops could play a crucial role in preserving cells until these gene therapies become clinically available.

To test whether the photoreceptors preserved by eye drop treatment are healthy enough for gene therapy to be effective, collaborators Valeria Marigo, Ph.D., and Andrea Bighinati, Ph.D., of the University of Modena, Italy, treated mice with gene therapy at the end of the one-week eye drop treatment. The gene therapy preserved vision for at least six additional months.

To determine whether the eye drops could work in humans—without conducting direct human tests—the researchers collaborated with Natalia Vergara, Ph.D., of the University of Colorado Anschutz in Aurora, to test the peptides in a human retinal tissue model of retinal degeneration. Cultured in dishes from human cells, the retinal-like tissue was exposed to chemicals that induced high levels of cellular stress. Without the peptides, the cells in the tissue model died quickly, but with the peptides, the retinal tissue remained viable. These human tissue data are a key first step toward human testing of the eye drops.

The research was funded by the NEI Intramural Research Program. Additional funding was provided by the Prevention of Blindness Society, Fondazione Telethon, HEAL-ITALIA Foundation, CellSight Development Fund, and Research to Prevent Blindness.

The NEI leads the federal government's research on the visual system and eye diseases. It supports basic science and clinical programs aimed at developing sight-preserving treatments and meeting the specific needs of people with low vision. For more information, visit https://www.nei.nih.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, comprises 27 institutes and centers and is part of the U.S. Department of Health and Human Services. NIH is the primary federal agency that conducts and supports basic, clinical, and translational medical research, and studies the causes, treatments, and cures for common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

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