Microglia implicated in inherited retinitis pigmentosa

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.

Results

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.

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