Clean-up cells munch through photoreceptors in retinitis pigmentosa

Scientists at the USA’s National Eye Institute have found a new way to tackle blinding eye conditions. Cells in the brain, spinal cord and eye that usually help by clearing up waste and fighting infection can also speed up damage to the light-sensitive part of the eye. The cells – called microglia – could make a good target for treatment to slow down sight loss.

Retinitis pigmentosa is the most common inherited eye condition, affecting 1 in 4000 people. First it kills off the light-detecting ‘photoreceptor’ cells that we use for side vision (called ‘rods’), then later it affects the central photoreceptors we use for detailed and colour vision (the ‘cones’).

One fix for all?

It’s caused by faults in any of around 100 genes, and those are just the ones we know about so far. Gene therapy to replace the faults could be one approach, but you would need a different fix for each gene. Targeting microglia could be a better alternative because it doesn’t matter which genetic fault is involved.

Dr Wai Wong and team studied mice with a genetic fault that causes retinitis pigmentosa in humans. In the early stages of the condition, the team saw that microglia were invading a layer of the retina near the photoreceptors that they usually keep out of.

Then the microglia surrounded the photoreceptors and ‘ate’ them in a process called phagocytosis (pronounced fay-jo-sigh-toe-sis). You can see it happen in this speeded-up video. In reality, the whole thing takes about an hour.

Phagocytosis is usually a healthy process to clear away dead cells. But in this case the microglia ate live photoreceptors too, if the photoreceptors were damaged.

The team showed that the rate of rod cell death slowed down in mice without microglia and they kept their vision for longer. A chemical compound to prevent phagocytosis also had a similar effect. Microglia seemed to ignore the cone cells altogether, which fits with what we know about how retinitis pigmentosa develops.

Find me! Eat me!

Results published in EMBO Molecular Medicine also showed that genetically faulty photoreceptors send out chemical signals to say “find me”. This calls in the microglia, which not only turn up and devour the photoreceptor but send out their own signals to attract even more microglia and trigger inflammation.

Dr Dolores M Conroy, Director of Research at Fight for Sight, said:

“Focusing on microglial cells as a new therapeutic target is a really interesting approach. I look forward to results from the National Eye Institute clinical trial which is underway and due to finish next year. They are testing the anti-inflammatory drug minocycline to find out whether it can stop microglia from becoming active.

“If so, this could be important not just to developing a treatment for retinitis pigmentosa but for any retinal disorders that cause photoreceptor loss.”