The brain’s ability to adapt and rewire itself throughout life continues to amaze neuroscientists. Researchers have found a way to restore sight to adult mice suffering from a form of congenital blindness, despite the relative maturity of rodents.
The mice modeled a rare human disorder of the retina of the eye, called Leber congenital amaurosis (ACL), which often causes blindness or severe visual impairment at birth.
This inherited condition appears to be caused by a mutation in one of dozens of genes associated with the retina and its light-sensing abilities.
Researchers have been working for several decades on treatments that could 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 all boost vision with varying levels of success, but synthetic compounds that target the retina seem particularly promising for those with mutations involving rod photoreceptors.
Rods are the photoreceptors at the back of the eye that detect dim light. These specialized neurons use a series of biochemical reactions to convert sensory light into electrical signals for the rest of the brain to “read”.
As the light-sensitive pigments in the retinal rods absorb low levels of light, they convert the retinal 11-cis molecule into all-trans-retinal, which in turn generates an impulse that descends from the optic nerve to the brain.
Previous studies on children with ACL have shown that synthetic retinoid treatments can help compensate for some vision loss when injected directly into the eye. But the impact of these treatments on adults with the disease is not as well understood.
“Although progress has been made, it remains unclear to what extent adult visual circuitry 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, the brain’s visual system is thought to form and strengthen during certain developmental windows in early life. If the eye is not exercised during these critical times, the brain’s visual networks may never be properly wired for sight, leading to lifelong vision deficits.
But a mammal’s vision potential may not be so rigidly wired; it could be much more plastic than expected.
To explore this idea, the researchers administered a synthetic retinoid for seven days to adult rodents born with retinal degeneration.
The treatment was ultimately successful in partially restoring the animals’ light sensitivity and typical light-orienting behaviors for 27 days.
Nine days after treatment, many more neurons in the visual cortex were 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 amazed at how well the treatment rescued the brain circuits involved in vision,” says neurobiologist Sunil Gandhi from the University of California at Irvine.
“Seeing involves more than intact, functioning retinas. It begins in the eye, which sends signals throughout the brain. It is in the brain’s central circuitry that visual perception actually occurs.”
The study was only conducted in mice, but the finding has neuroscientists thinking that the critical window for the human visual system may also be larger than previously thought.
In other words, a lack of vision in childhood does not necessarily mean that sight can never be recovered in adulthood.
“Immediately after treatment, signals from the eye on the opposite side, which is the dominant pathway in mice, activated twice as many neurons in the brain,” Ghandi explains.
“What was even more mind-blowing was that signals from the same-side eye pathway activated five times more neurons in the brain after treatment and this impressive effect was long-lasting.”
Further research in animal models is needed. But perhaps one day neuroscientists can test whether similar benefits could be triggered in older humans with certain versions of ACV.
“The fact that this processing works so well in the central visual pathway in adulthood supports a new concept that there is a latent potential for vision just waiting to be triggered,” says Ghandi.
The study was published in Current biology.