NIH research points to microglia as potential therapeutic target in retinitis pigmentosa
Spider-like cells inside the brain, spinal cord and eye hunt for invaders, capturing and then devouring them. These cells, called microglia, often play a beneficial role by helping to clear trash and protect the central nervous system against infection. But a new study by researchers at the National Eye Institute (NEI) shows that they also accelerate damage wrought by blinding eye disorders like retinitis pigmentosa (RP). The findings were published in the journal EMBO Molecular Medicine.
Lead investigator, Wai T. Wong M.D., Ph.D., chief of the Unit on Neuron-Glia Interactions in Retinal Disease at NEI, and his team studied mice with a mutation in a gene that can also cause RP in people. The researchers observed in these mice that very early in the disease process, the microglia infiltrate a layer of the retina near the photoreceptors, called the outer nuclear layer, where they don’t usually venture. The microglia then create a cup-like structure over a single photoreceptor, surrounding it to ingest it in a process called phagocytosis. Wong and his team caught this dynamic process on video. The whole feast, including digestion, takes about an hour.
Phagocytosis is a normal process in healthy tissues and is a key way of clearing away dead cells and cellular debris. However, in RP the researchers found that the microglia target damaged but living photoreceptors in addition to dead ones. The microglia seem to ignore cone photoreceptors, which fits with the known early course of RP.
“These findings suggest that therapeutic strategies that inhibit microglial activation may help decelerate the rate of rod photoreceptor degeneration and preserve vision,” Wong said.
A clinical trial (NCT02140164) is already underway at NEI to see if the anti-inflammatory drug minocycline can block the activation of microglia and help slow the progression of RP. (Editor’s note: Minocycline has been seen in cell culture to also protect retinal cells from oxidative damage. This finding suggests that minocycline, too, may play a therapeutic role in the treatment of age-related macular degeneration.)
Wong’s lab colleagues Lian Zhao, Ph.D., Matthew Zabel, Ph.D., and Xu Wang, M.D., Ph.D., played key roles in conceiving and conducting the RP research. To hear Zabel talk about his work on RP, watch this video from NIH and LabTV.
NEI leads the federal government’s research on the visual system and eye diseases. NEI supports basic and clinical science programs that result in the development of sight-saving treatments. For more information, visit http://www.nei.nih.gov.