Scientists at the National Institutes of Health (NIH) have developed a new surgical technique that allows multiple tissue grafts to be implanted into the retina of the eye. The results from animal studies could help improve treatment options for dry age-related macular degeneration (AMD), which is a leading cause of vision loss in older people. A report on the technique was published in JCI Insight.
Dry Macular Degeneration: What the New Technique Can Do
In diseases such as dry macular degeneration, the light-sensitive retinal tissue at the back of the eye degenerates. Scientists are testing therapies to restore damaged retinas using transplants made from tissue grown in the laboratory from the patient’s own stem cells. Until now, surgeons could only insert one graft into the retina, which limited the treatable area in patients and also made it difficult to compare individual animal models. Such comparisons are crucial to confirm that the tissue grafts connect to the retina and the underlying blood supply from a network of tiny blood vessels called the choriocapillaris.
For this technique, the researchers developed a new surgical clamp that maintains eye pressure during the immediate sequential insertion of two tissue patches while minimizing damage to the surrounding tissue. In animal models, the scientists used their newly developed surgical technique to compare two different grafts inserted sequentially into the same experimentally induced AMD-like lesion. One graft consisted of retinal pigment epithelial (RPE) cells grown on a biodegradable scaffold. RPE cells support and nourish the light-sensitive photoreceptors of the retina.
In addition to the loss of RPE cells and photoreceptors, AMD leads to a loss of vision. In the laboratory, RPE cells are cultivated from human blood cells after these have been converted into stem cells. The second transplant consisted only of the biodegradable scaffold and served as a control. After the operation, the scientists used artificial intelligence to analyze retinal images and compare the effects of the two transplants. They observed that the RPE grafts promoted photoreceptor survival, while photoreceptors in the vicinity of grafts consisting only of the scaffold died at a much higher rate. In addition, they were able to confirm for the first time that the RPE graft also regenerated the choriocapillaris, which supplies the retina with oxygen and nutrients. The results extend the possibilities shown in an ongoing NIH-led first-in-human clinical trial of RPE grafts from patients for the dry form of AMD.
Treatment Options for Wet Macular Degeneration
Dry age-related macular degeneration accounts for about 80% of all AMD cases and occurs when the macula, a part of the retina, thins, leading to a buildup of proteins and cell death that blurs a person’s central vision. Wet AMD, also known as neovascular AMD, is caused by the growth of new blood vessels that invade the retina, an area normally free of vascular activity. Research on mice at Ohio State University suggests that there may be an alternative treatment for the “wet” form of age-related macular degeneration (AMD).
The only currently available treatment for wet AMD is the injection of a drug into the eye that inhibits the activity of a growth factor protein called VEGF, which is known to promote the formation of abnormal blood vessels in this disease. Anti-VEGF treatment has disadvantages – after two years, around half of patients no longer respond to it. Patients may also develop scars under the retina.
Researchers have discovered in mice that an enzyme associated with cell growth and division is responsible for the invasion of blood vessels in the back of the eye, which leads to blurred vision in the center of the visual field in wet AMD. By specifically inhibiting the enzyme, known as telomerase, with an experimental drug, the abnormal vascular growth in the retina of the animals could be suppressed. Research in this area aims to make current therapies as effective as possible, identify new therapies and prevent people from developing wet AMD in the first place.