Researchers at the National Institutes of Health (NIH) in the United States say they have developed eye drops that extend vision in animal models of a group of inherited diseases that lead to progressive vision loss in humans, known as retinitis pigmentosa.
According to a report on the study, published in Communications Medicine, 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), which helps preserve cells in the eye’s retina.
Dr Patricia Becerra, chief of NIH’s Section on Protein Structure and Function at the National Eye Institute and senior author of the study, said the study had not produced a cure, but 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 (AMD)”.
“Given these results, we’re excited to begin trials of these eye drops in people.”
All degenerative retinal diseases have cellular stress in common. While the source of the stress may vary – dozens of mutations and gene variants have been linked to retinitis pigmentosa, AMD, and other disorders – high levels of cellular stress cause retinal cells to gradually lose function and die. Progressive loss of photoreceptor cells leads to vision loss and eventually blindness.
Previous research from Dr Becerra’s lab revealed that, in a mouse model, the natural protein PEDF can help retinal cells stave off the effects of cellular stress. However, the full PEDF protein is too large to pass through the outer eye tissues to reach the retina, and the complete protein has multiple functions in retinal tissue, making it impractical as a treatment.
To optimise the molecule’s ability to preserve retinal cells and to help the molecule reach the back of the eye, Dr Becerra developed a series of short peptides derived from a region of PEDF that supports cell viability. These small peptides can move through eye tissues to bind with PEDF receptor proteins on the surface of the retina.
Dr Becerra’s team created two eye drop formulations, each containing a short peptide. The first peptide candidate, called “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 eye’s surface were found in high concentration in the retina within 60 minutes, slowly decreasing over the next 24 to 48 hours. Neither peptide caused toxicity or other side effects.
When administered once daily to young mice with retinitis pigmentosa-like disease, H105A slowed photoreceptor degeneration and vision loss.
“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 researcher Ms Alexandra Bernardo-Colón.
To see whether the eye drops could work in humans – without actually testing in humans directly – the researchers worked with Dr Natalia Vergara, University of Colorado Anschutz, Aurora, to test the peptides in a human retinal tissue model of retinal degeneration.
Grown in a dish from human cells, the retina-like tissues were exposed to chemicals that induced high levels of cellular stress. Without the peptides, the cells of the tissue model died quickly, but with the peptides, the retinal tissues remained viable.
These human tissue data provide a key first step supporting human trials of the eye drops.
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