Now You See Them, Now You Don’t
Might temporary microglia depletion treat inflammatory retinal disease?
Mark Hillen |
Microglia are curious cells. They’re the retina’s (and the central nervous system’s) resident macrophages and when infection occurs, they’re the first line of defense. But they’re also central to keeping neurons healthy – in addition to looking for pathogens, they constantly scavenge for plaques and damaged neurons or synapses, always ready to transform into reactive phagocytes. But there’s strong evidence that microglial reactivity is a hallmark of various retinal degenerative and inflammatory diseases, including both rare genetic disorders like retinitis pigmentosa (RP) and X-linked juvenile retinoschisis, and more common multifactorial retinal diseases such as AMD, diabetic retinopathy, glaucoma, and uveitis. Why? It seems that retinal microglia, in disease states, can remove healthy cells too, contributing to vision loss. Studies have shown inhibiting or removing microglia in retinal degenerative disorders can help retain photoreceptors and slow vision loss. But then, they play an important role in maintaining a healthy retina. So, is their inhibition or removal ultimately bad news in the long-term too?
Wai Wong, chief of the US National Eye Institute’s Section on Neuron-Glia Interactions in Retinal Disease, and his team set out to find out more about retinal microglia – and what happens to the retinal if you eliminate them (in mice). To do this, Wong and his team used PLX5622, a drug that blocks the microglial cell survival receptor, CSF-1. Over a period of several days, CSF-1 inhibition strips microglia almost entirely from the retina, leaving just a few cells clustered around the optic nerve. Crucially, the loss of microglia doesn’t affect nerve function. And, as Wong notes, “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.”
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