The brain's ability to adapt and rewire itself throughout life astounds neuroscientists. Researchers have found a way to restore vision in adult mice with congenital blindness, despite the mice's relative maturity.
The mice were modeling a rare human disorder of the retina of the eye, called Leber congenital amaurosis (LCA), which causes blindness or severe visual impairment at birth.
This genetic condition appears to be caused by a mutation in any one of dozens of genes involved in the retina and its light-sensing abilities.
Researchers have been working for decades on treatments that can restore damaged or dysfunctional photoreceptors in this part of the eye. Some strategies include retinal implants, gene editing interventions, and drug treatments.
These emerging therapies improve vision with varying degrees of success, but synthetic compounds targeting the retina appear particularly promising for those with mutations involving rod photoreceptors.
Rods are photoreceptors at the back of the eye that sense dim light. These specialized neurons use a series of biochemical reactions to convert sensory light into electrical signals to 'read' the rest of the brain.
Light-sensitive pigments in retinal rods absorb small amounts of light, converting the 11-cis retinal molecule to all-trans-retinal, which 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 ability to see may not be so hard-wired; It can be much 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, more neurons in the visual cortex were being activated by the optic nerve. This suggests that 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 an intact and functioning retina. It starts in the eye, which sends signals throughout the brain. It's in the brain's central circuits where visual perception actually occurs." The study was conducted only in mice, but the findings lead neuroscientists to think that the critical window of 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.
