It’s a mystery that has confounded scientists for many years: Why don’t mice with Usher syndrome type 1 — one of three types of combined blindness and deafness in humans — lose vision? It is an important question, because mouse models help us understand how vision is lost and how effective treatments might be. But if the mouse isn’t losing vision, how can we tell if a potential vision-saving therapy is working?
Researchers from the Institut de la Vision in Paris, France, have taken a big step in unraveling this mystery. In a recent paper, published in the Journal of Cell Biology, they reported that, in humans, Usher 1 proteins are prevalent near a girdle-like structure, known as a calyceal process, which wraps around the middle of photoreceptors.
Usher syndrome type 1 occurs if any of these proteins are missing or defective. However, normal mice have neither the girdle nor the abundance of Usher 1 proteins in that region of their photoreceptors, making them an inadequate model of human Usher 1 disease.
Traditionally, testing emerging therapies in animal models has been an important first step before evaluating them in humans. As the Usher 1 mouse illustrates, animal models have their limitations.
The answer to this problem, as the French researchers note, may be induced pluripotent stem cells (iPSC). Scientists have found a way to take a small skin or blood sample from a patient, turn back the clock on those sample cells so they become stem cells, and then coax them forward to become photoreceptors, or any other cell type in the body. And voila! — we have a model of human retinal disease that we can study in a dish. We can even use the new cells to test drugs and gene therapies.
Keep in mind that iPSC won’t be a complete replacement for an animal model; we still need a complete biological system for testing safety. But human iPSC greatly improve our ability to understand disease and test potential therapies.
What’s even more exciting is that researchers are using induced pluripotent stem calls to make new photoreceptors and other retinal cells, which can be transplanted back into the patient to replace those cells lost to retinal disease.
The therapeutic potential for iPSC is so big, a Japanese researcher just won a Nobel Prize for discovering them.
Above: detail image of a retina, with photoreceptors in green.