Retinal microglia contribute to rod demise in retinitis pigmentosa—a blinding hereditary retinal disease for which there is currently no approved treatment, according to a recent study.
Typically, rod photoreceptors in retinitis pigmentosa degenerate as a result of genetic mutations. Unfortunately, more than 100 possible diverse genes have been implicated, which means that gene therapy—while promising—remains a distant and impractical dream in many cases.
Results of this new study—published in EMBO Molecular Medicine—raise the prospect of retinal microglia providing a future target for novel therapeutic approaches that will defer photoreceptor loss and associated loss of vision.
Microglia—glial cells that function as macrophages in the central nervous system—represent the endogenous brain defence and immune system. Microglial migration is essential for immune defence and wound healing, and microglial phagocytosis plays a key role in removing apoptotic cells.
In response to a neurological lesion, microglia accumulate at the damaged site and remove cellular debris and even parts of damaged cells. Further, it has recently been discovered that microglial phagoptosis (phagocytosis of a living cell) is also a primary cause of neuronal cell death.
Researchers led by Wai T. Wong, MD, PhD—chief, neuron-glial interactions in retinal diseases, National Eye Institute, National Institutes of Health, Bethesda, MD—examined interactions between retinal microglia and photoreceptors throughout the course of retinal degeneration to uncover the underlying cellular mechanisms involved.
They primarily studied mice with a mutation in the rod photoreceptor gene Pde6b that is known to also cause retinitis pigmentosa in humans.
In retinitis pigmentosa, the mutations induce cellular stress in non-apoptotic rod photoreceptors and cause the production of phatidylserine, which is known as the ‘eat-me’ signal. This marks the rod as a target for phagocytosis by the microglia, even though the cell—if left alone—would continue to be viable.