Basic Science

Could a blind eye regenerate?

Imagine that day by day, your field of vision becomes slightly smaller, narrowing or dimming until eventually you go completely blind. We tend to think of blindness as something you’re born with, but in fact, with many diseases like Retinitis pigmentosa and Usher syndrome, blindness can start developing when you’re a kid, or even when you’re an adult. Both of these rare genetic diseases affect the retina, the screen at the back of the eye that detects light and helps us see. Now imagine if the eye could regenerate itself so that a blind person could see again. To understand if that’s possible, we need to grasp how the retina works and what it has to do with a multitalented creature named the zebrafish. The human retina is made of different layers of cells, with special neurons that live in the back of the eye called rod and cone photoreceptors. Photoreceptors convert the light coming into your eye into signals that the brain uses to generate vision. People who have Usher syndrome and retinitis pigmentosa experience a steady loss of these photoreceptors until finally that screen in the eye can no longer detect light nor broadcast signals to the brain. Unlike most of your body’s cells, photoreceptors don’t divide and multiply. We’re born with all the photoreceptors we’ll ever have, which is why babies have such big eyes for their faces and part of why they’re so cute. But that isn’t the case for all animals. Take the zebrafish, a master regenerator. It can grow back its skin, bones, heart and retina after they’ve been damaged. If photoreceptors in the zebrafish retina are removed or killed by toxins, they just regenerate and rewire themselves to the brain to restore sight. Scientists have been investigating this superpower because zebrafish retina are also structured very much like human retina. Scientists can even mimic the effects of disorders like Usher syndrome or retinitis pigmentosa on the zebrafish eye. This allows them to see how zebrafish go about repairing their retinas so they might use similar tactics to fix human eyes one day, too. So what’s behind the zebrafish’s superpower? The main players are sets of long cells that stretch across the retina called Müller glia. When the photoreceptors are damaged, these cells transform, taking on a new character. They become less like Müller cells and more like stem cells, which can turn into any kind of cell. Then these long cells divide, producing extras that will eventually grow into new photoreceptors, travel to the back of the eye and rewire themselves into the brain. And now some researchers even think they’ve found the key to how this works with the help of one of two chemicals that create activity in the brain called glutamate and aminoadipate. In mouse eyes, these make the Müller glia divide and transform into photoreceptors, which then travel to the back of the retina, like they’re replenishing a failing army with new soldiers. But remember, none of this has happened in our retinas yet, so the question is how do we trigger this transformation of the Müller glia in the human eye? How can we fully control this process? How do photoreceptors rewire themselves into the retina? And is it even possible to trigger this in humans? Or has this mechanism been lost over time in evolution? Until we tease apart the origins of this ability, retinal regeneration will remain a mysterious superpower of the common zebrafish.

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