Biomedical research has led to both increased knowledge of many diseases and treatments that improve outcomes for patients. This includes research into age-related macular degeneration (AMD). Scientists at the National Institutes for Health (NIH) and Washington University at St. Louis have developed separate techniques that can lead to improved treatments for this disease.
Scientists at NIH developed a new technique for surgically implanting multiple tissue grafts in the eye’s retina. Using animal models, they designed a new surgical clamp that maintains eye pressure during the insertion in the retina of two tissue grafts grown in the lab from patient-derived stem cells. Previously, surgeons were only able to place one graft in the retina, which limits both the area that can be treated and the ability to do side-by-side comparisons in the animal models. These comparisons are essential for confirming that the grafts are integrating with the retina and the eye’s network of blood vessels, known as choriocapillaris.
This clamp allowed for the insertion of two tissue patches in immediate succession while reducing damage to the surrounding tissue. This technique allowed researchers to compare the two grafts placed sequentially in the same experimentally generated AMD-like lesion. One graft was made of retinal pigment epithelial (RPE) cells grown on a biodegradable scaffold. The RPE cells nourish the retina’s light-sensing photoreceptors. The second graft was the biodegradable scaffold to serve as a control.
After the surgery, scientists used AI to analyze retinal images and to compare each graft. They saw that the RPE grafts helped improve the survival of the photoreceptors and the RPE grafts were able to regenerate the choriocapillaris, which supplied the retina with oxygen and nutrients. In comparison, the photoreceptors near the scaffold only grafts died at a higher rate.
Of course, it would be great if there was a way to prevent or at least slow the progression of AMD. A study at Washington University School of Medicine in St. Louis discovered a possible way to slow or block the progression of AMD. Researchers discovered problems with cholesterol metabolism in this kind of vision loss. This could help explain the link between AMD and cardiovascular disease.
The study found that increasing amounts of a molecule called apolipoprotein M (ApoM) in both human plasma samples and mouse models of macular degeneration, fixes the problem of cholesterol processing. Problems with cholesterol processing led to cellular damage in the eye and other organs. Researchers think that increasing the amount of ApoM could be used as a treatment for AMD, as well as some forms of heart failure that are caused by problems in cholesterol processing.
Since current treatments that reduce the chance of vision loss from AMD are limited for use during the most advanced stages of the disease, finding a way to increase ApoM levels could treat or even prevent the disease from developing and preserve vision. When someone has AMD, eye doctors can see cholesterol deposits under the retina. While vision might be normal during the early stages of AMD, the deposits increase inflammation and contribute to the gradual loss of central vision.
Since increased levels of ApoM can be used to successful treat AMD, researchers wanted to see if they could reverse the harmful effects of low ApoM. They increased the levels of ApoM in mouse models of AMD with genetic modification or plasma transfer from other mice. The mice with increased the levels of ApoM had improved retinal health, enhanced function of light-sensing retina cells and reduce cholesterol deposits. In addition, scientists found that ApoM triggers a signaling pathway that breaks the cholesterol into cellular compartments called lysosomes. The lysosomes play an important role in getting rid of cellular waste.
Once again research is pushing the boundaries of what is possible when it comes to treating an eye disease like AMD. The end results are improved treatments for this disease and improved outcomes for patients.
https://medicine.washu.edu/news/strategy-to-prevent-age-related-macular-degeneration-identified/