Scientists at the Medical College of Georgia have demonstrated that retinal disease initiates increased communication between endothelial cells and nearby microglia. Specifically, the team found that the communication between the two promotes excessive inflammation and the development of dysfunctional capillaries that lead to retinal detachment. Their results were published in Science Translational Medicine.
"The reciprocal interaction between macrophages and (endothelial cells) promotes a feed-forward relationship that strongly augments angiogenesis," says lead researcher Yuqing Huo. In low oxygen environments, endothelial cells produce more lactate, but also biochemical markers that encourage nearby microglia to be more active, they explain. Normally supportive immune cells also begin overproducing inflammation-promoting factors that promote angiogenesis. The result is pathological angiogenesis, a major cause of irreversible blindness in diabetic retinopathy, retinopathy of prematurity, or age-related macular degeneration.
Through their efforts to understand how the conversations between the two cells can be destructive, the team identified promising checkpoints. When one of the most potent activators of glycolysis—called Pfkfb3—is removed from the microglia, lactate production clearly goes down and the cells no longer aid the production of dysfunctional capillaries. Conversely, the expression of both the messenger RNA that enables the production of Pfkfb3 and lactate is significantly higher in the cells when oxygen levels are low.
"This is a major problem in our country, loss of vision because of compromised oxygen for a variety of reasons," says the study's first author Zhiping Liu. "We hope this additional insight into how that process destroys vision, will enable us to find better ways to intervene.”