Researchers, based at the Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute in Bethesda, MD, have shown that microglia in the retina of animal models can undergo repopulation leading to a renewal of organization and function. The discovery may have relevance for the development of therapeutic strategies to control inflammation and slow the progression of retinal disorders such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Commenting on the research achievement, the lead investigator of the study, Wai T. Wong, M.D., Ph.D., stated, “neuroinflammation is an important driver of the death of neurons in retinal diseases. Our study is foundational for understanding ways to control the immune system in the retina.”
Retinal microglia are specialized immune cells that maintain healthy neuronal function and, as immune cells, can migrate rapidly to the site of injury to remove unhealthy and dying neurons, although on occasion healthy cells may also be removed. Balancing the protective and destructive characteristics of such function is a potentially valuable avenue for research. The Bethesda research team were interested to understand how the retina responded to the elimination of microglia in the retina, and how the retina might organize the arrangement and function of returning microglia so as to maintain renewed biological function. Artificially removing microglia for short periods of time does not appear to affect retinal function and so depletion of such cells may be mediated temporarily in order to reduce inflammation, thereby providing a therapeutic intervention that would avoid long term adverse effects on the retina. According to Dr. Wong, “if we were to get rid of the microglia while a large, inappropriate immune response was happening, we might be able to miss the worst of the inflammation, but still come back into balance at a later point in time. We could hit pause on the immune system in the retina in a directed way.”
Having removed the microglia the research team were able to demonstrate that the microglia complement became fully restored within 150 days of microglia removal. The returning microglia were inititally seen to develop in clusters close to the optic nerve but gradually the repopulation of the cells spread outwards toward the retinal periphery until an even redistribution was established both across and throughout the various retinal layers. With the restored organization the researchers were able to detect restored function, activation and migration of the new cells to sites of induced injury, in addition to which, such cellular activity appeared to correlate with functional ERG improvement. While additional research will be needed to deliver a local retinal formulation, the basic principle appears to indicate the validity of the approach for controlling inflammation, and thereafter slowing progression of disease in a number of ocular indications.