Scientists Give Back Sight to Blind Mice with New Therapy

Hereditary blindness can be caused by a progressive degeneration of the light-sensing cells in the eye, the photoreceptors. This condition impacts millions of people worldwide; now, though, scientists have managed to restore sight to blind mice with this particularly condition.

When the light-sensing cells degenerate, cells in deeper layers of the retina, which normally cannot sense light, remain intact. In this latest study, the researchers focused on the technique known as "optogenetics." This introduces light-sensing proteins into these surviving retinal cells and turns them into replacement photoreceptors. Until now, though, scientists couldn't use traditional light-sensitive proteins, since they require unnaturally high and potentially harmful light intensities.

"We were asking the question, 'Can we design light-activatable proteins that gate specific signaling pathways in specific cells?', in other words, can the natural signaling pathways of the target cells be retained and just modified in a way to be turned on by light instead of a neurotransmitter released from a preceding neuron?" said Sonja Kleinlogel, one of the researchers, in a news release.

The aim was to essentially achieve maximal compatibility with native signaling while retaining all of the advantages of traditional optogenetic proteins.

The novel light-sensing protein, called Opto-mGluR6, is a chimeric protein composed of the light-sensing domains of the retinal photopigment melanopsin and the ON-bipolar cell-specific metabotropic glutamate receptor mGluR6, which is naturally activated by glutamate released from the photoreceptors and amplifies the incoming signal through a coupled intracellular enzymatic pathway. The response strength of Opto-mGluR6 never attenuates, no matter how often and hard the protein is hit by light.

In this study, the scientists targeted the retinal ON-bipolar cells. They turned the native chemical receptor, mGluR6, into light-activated receptors. This ensured the conservation of native signaling within the ON-biopolar cells.

"The major improvement of the new approach is that patients will be able to see under normal daylight conditions without the need for light intensifiers or image converter goggles, and retaining the integrity of the intracellular enzymatic cascade through which native mGluR6 acts ensures consistency of the visual signal, as the enzymatic cascade is intricately modulated at multiple levels," said Kleinlogel.

The findings are published in the journal PLOS Biology.

For more great science stories and general news, please visit our sister site, Headlines and Global News (HNGN).