New discovery could pave the way for restoring sight in adults with congenital blindness

Developing a cure for adults

Researchers have long been working on developing treatment methods for damaged or dysfunctional photoreceptors.

According to previous studies conducted on children with LCA, synthetic retinoid treatments that are injected directly into the eye can help restore some vision loss. However, how these therapies affect adults is still not clear enough.

"Frankly, we were blown away by how much the treatment rescued brain circuits involved in vision," said Sunil Gandhi, professor of neurobiology and behavior and the corresponding author.

"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."

Until recently, scientists thought that in order for the brain's central circuits to wire themselves properly, those signals had to be received during childhood. However, the results of the current study, which employed rodent models of LCA, were surprising.

“The central visual pathway signaling was significantly restored in adults, especially the circuits that deal with information coming from both eyes,” Gandhi said.

“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. 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. The restoration of visual function at the level of the brain was much greater than expected from the improvements we saw at the level of the retinae. 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.”

According to Gandhi, these new findings could pave the way for the development of retinoid therapies to fully restore the central visual pathway in adults suffering from this illness.

The study was published in the journal Current Biology.

Abstract:

Despite the recent emergence of multiple cellular and molecular strategies to restore vision in retinal disorders, it remains unclear to what extent central visual circuits can recover when retinal defects are corrected in adulthood. We addressed this question in an Lrat−/− mouse model of Leber congenital amaurosis (LCA) in which retinal light sensitivity and optomotor responses are partially restored by 9-cis-retinyl acetate administration in adulthood. Following treatment, two-photon calcium imaging revealed increases in the number and response amplitude of visually responsive neurons in the primary visual cortex (V1). In particular, retinoid treatment enhanced responses from the ipsilateral eye, restoring the normal balance of eye-specific responses in V1. Additionally, the treatment rescued the modulation of cortical responses by arousal. These findings illustrate the significant plasticity of the adult central visual system and underscore the therapeutic potential of retinoid administration for adults with retinal diseases.