Scientists 'Blown Away' by New Treatment Restoring Sight to Blind Mice

The brain's ability to adapt and rewire itself throughout life continues to surprise neuroscientists. Researchers have found a way to restore sight in adult mice with a form of congenital blindness, in spite of the rodents' relative maturity.

The mice were modeling a rare human disorder of the eye's retina, called leber congenital amaurosis (LCA), which often causes blindness or severe visual impairment at birth.

This inherited condition seems to be caused by a mutation in any one of dozens of genes associated with the retina and its light-sensing abilities.

Researchers have been working on treatments that could restore damaged or dysfunctional photoreceptors in this part of the eye for several decades. Some strategies include retinal implants, gene editing interventions, and drug treatments.

These emerging therapies all boost vision with varying levels of success, but synthetic compounds that target the retina look particularly promising for those with mutations that involve rod photoreceptors.

Rods are the photoreceptors at the back of the eye that sense dim light. These specialized neurons utilize a series of biochemical reactions to convert sensory light into electrical signals for the rest of the brain to 'read'.

As light-sensitive pigments in retinal rods absorb low levels of light, they convert the molecule 11-cis retinal into all-trans-retinal, which in turn generates an impulse that travels down the optic nerve to the brain.

Previous studies on children with LCA have shown that synthetic retinoid treatments can help compensate for some vision loss when injected straight into the eye. But how these treatments impact adults with the condition is not as well understood.

"Although some progress has been made, it still remains unclear the extent to which adult visual circuits can be restored to a fully functional state at the level of the visual cortex upon correction of the retinal defect," the researchers write.

Traditionally, it's been thought that the brain's visual system is formed and strengthened during certain developmental windows in early life. If the eye isn't being exercised during these critical periods, then visual networks in the brain may never be wired properly for sight, leading to lifelong deficits in vision.

But a mammal's potential for vision may not be so rigidly wired; it could be far more plastic than assumed.

To explore this idea, researchers administered a synthetic retinoid for seven days to adult rodents born with retinal degeneration.

The treatment was ultimately successful at partially restoring the animals' light sensitivity and their typical light-orienting behaviors for 27 days.

Nine days after treatment, far more neurons in the visual cortex were being activated by the optic nerve.

This suggests the central visual pathway that carries information from the eye to the visual cortex can be significantly restored by retinoid treatment, even in adult mice.

"Frankly, we were blown away by how much the treatment rescued brain circuits involved in vision," says neurobiologist Sunil Gandhi from the University of California, Irvine.

"Seeing involves more than intact and functioning retinae. It starts in the eye, which sends signals throughout the brain. It's in the central circuits of the brain where visual perception actually arises."

The study was only conducted among mice, but the discovery has neuroscientists thinking that the critical window for the human visual system may also be larger than once assumed.

In other words, a lack of vision in childhood does not necessarily mean sight can never be recovered in adulthood.

"Immediately after the treatment, the signals coming from the opposite-side eye, which is the dominant pathway in the mouse, activated two times more neurons in the brain," says Ghandi.

"What was even more mind-blowing was that the signals coming from the same-side eye pathway activated five-fold more neurons in the brain after the treatment and this impressive effect was long-lasting."

Further research on animal models is needed. But perhaps one day, neuroscientists can test whether similar benefits could be triggered in older humans with some versions of LCA.

"The fact that this treatment works so well in the central visual pathway in adulthood supports a new concept, which is that there is latent potential for vision that is just waiting to be triggered," Ghandi explains.

The study was published in Current Biology.

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