The eye is unique in that it doesn’t follow the usual path when it comes to immune response. One scenario involves a specific protein that regulates the vascular barrier. This in turn weakens a signaling system, it lower levels of another protein and this can damage protective barriers in the brain and eyes. Another scenario is when injury or disease occurs and specific immune cells, known as neutrophils, are not called in to help. Why do these things happen and what can be done about them?
Two research projects, one at University of Minnesota Medical School and the other at the Del Monte Institute for Neuroscience at the University of Rochester, are looking to learn about these scenarios and their implications for vision health.
Work done at the University of Minnesota Medical School found that a cancer signaling pathway, known as the Norrin/Frizzled4 signaling pathway is linked to MDM2–p53 axis, which suppresses tumors. Researchers found that p53 weakens the Norrin signaling system in blood vessels by lowering another protein, NCAPH.
This suggests that drugs that boost p53 levels, namely MDM2 inhibitors, may damage the protective barriers in the brain and eyes. This study also draws attention to NCAPH as a gene linked to familial exudative vitreoretinopathy (FEVR), a rare, inherited eye condition that affects blood vessel growth in the retina.
Since p5 is critical in the regulating the vascular barrier function, it is important to study whether MDM2 inhibitors could negatively affect the blood retina barrier. This finding also supports the need for additional study into the role of NCAPH in the endothelial cells, both in its downstream role of p53 and as a disease gene in disorders, such as FEVR.
Research done at Del Monte Institute for Neuroscience at the University of Rochester found that the retina responds differently when an infection or injury occurs. In particular, when the photoreceptor cells in the retina are damaged, the brain’s immune cells, known as microglia, respond. Yet, another type of immune cell, the neutrophils, which does respond when others parts of the body get an infection, is not called into action.
Scientists wanted to learn why this happens, since this affects millions of people who experience vision loss through the loss of photoreceptors. They studied the retinas of mice with photoreceptor damage and saw that both neutrophil and microglia cells are present in the retina. Yet, only the microglia cells respond to the injury and they do not signal for the neutrophils to help. Scientists think this is a type of cloaking that happens when the retina is injured as a way to protect it from wave of immune cells that would do more harm than good.
These projects show both the unique responses that occur in the eye when it comes to maintaining the blood retina barrier and immune response when an infection or injury occurs. Knowing about these responses can lead to greater insights about diseases such as age-related macular degeneration and retinitis pigmentosa. These insights can lead to treatments that improve outcomes for those who have these diseases.