A glimpse of the future: sight restored in blind mice

A glimpse of the future: sight restored in blind mice

A promising new treatment for hereditary blindness uses optogenetics to introduce light-sensitive proteins into surviving retinal cells, turning them into replacements for degenerated photoreceptors.

Hereditary blindness affects millions of people worldwide and is caused by the progressive degeneration of rods and cones in the retina. Whilst the photoreceptors are lost, other cells deeper within the retina, known as ON-bipolar cells, still remain intact.

Dr Sonia Kleinlogel, corresponding author for of the paper, said: "The new therapy can potentially restore sight in patients suffering from any kind of photoreceptor degeneration, for example, those suffering from severe forms of age-related macular degeneration, a very common disease that affects to some degree about one in every 10 people over the age of 65."

Research recently published in the journal PLOS Biology showed that by introducing a novel light-sensitive protein into the surviving cells they could respond to light and thereby restore vision.

Classical optogenetic proteins, like channelrhodopsin or halorhodopsin, cannot be used for this therapy because they require potentially damaging light intensities and employ a different signalling mechanism within the cell after the light has been detected.

Creating a new therapy

To overcome this problem, the team of researchers from the Universities of Bern and Göttingen created a novel light-sensitive protein called Opto-mGluR6. This protein is made from the light-sensing domain of the retinal photopigment melanopsin and a cell-specific glutamate receptor native to the surviving cells of the retina (ON-bipolar cells). Glutamate is a neurotransmitter that is usually released from the photoreceptor cells to activate ON-bipolar cells.

This protein has a number of advantages. Firstly, the incoming signal is processed within the cell in the same way as the photoreceptor signal. Secondly, the melanopsin pigment is bleach resistant, so the response strength of the protein never diminishes. Finally, it is made from two proteins that are naturally present in the retina and so should not elicit an immune response.

Dr Kleinlogel added: "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."

The mGluR6 receptor belongs to a family of proteins called G-protein coupled transmembrane receptors (GPCRs). By making other light sensitive proteins made of a light-sensitive region and a GPCR, new therapies for other conditions such as pain, depression and epilepsy could also be developed.

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