There is a rare hereditary vision disease, involving defective copies of the CaBP4 gene, that causes poor vision starting in childhood. The protein made by the gene is crucial for chemical signaling in the retina.
It’s also something that can affect dogs — and by treating dogs, researchers have discovered a therapeutic approach that promises to be transformative.
In a study published in Advances in molecular therapyResearchers led by a team from the University of Michigan in the US report that a single-dose gene therapy treatment not only halted the progression of blindness, but also physically repaired damaged connections.
This raises the tantalizing prospect of treatments that can repair mammalian nerve cells, something many previously thought impossible.
“We were able to demonstrate three independent structural changes that promote plasticity in the adult retina,” explains veterinary ophthalmologist Billie Beckwith-Cohen of Michigan State University.
“Not only were new components added, but pre-existing anomalies were repaired.”
After identifying the CaBP4 gene as responsible for vision loss in a group of whippet dogs, researchers injected a harmless virus carrying a working copy of the gene into the animals’ retinas.
))>The treatment significantly improved the canines’ vision, particularly in dim light – where CaBP4 protein deficiency makes the most difference.
Additionally, the treated regions of the retina deteriorated less and the outer plexiform layer (OPL) that contains crucial visual connectors grew significantly, as did the synaptic ribbons inside the eye’s photosensitive cells.
The growth of the OPL and synaptic ribbons is delayed when the CaBP4 gene does not function properly, which researchers liken to errors in a construction plan.
“One can essentially discuss retinal gene mutations as a typo in a plan that makes the instructions incomprehensible to the system, leading to faulty design and subsequent vision loss,” says Beckwith-Cohen. “Our therapy essentially provides new instructions for the misspelled segment, like an editor.”
The study is the result of a decade of research into these eye conditions, and while it remains to be seen whether the same approach would work in humans, the team is confident it would translate.
“Our results show that gene therapy is not only capable of restoring retinal function, but also of establishing a near-normal anatomical arrangement in the OPL of the retina,” the researchers write in their published article.
“This recovery involves the expansion of a layer that did not form normally during retinal development as well as the maturation of synaptic features such as ribbon elongation, supporting the enduring pattern of the retinal neural network into adulthood.”
Although CaBP4 gene disease is rare in humans and dogs, the researchers suggest that the findings could lead to other methods for repairing damaged neural networks and treating a wider range of diseases.
Even after significant eye growth retardation and subsequent damage to nerve cell connections, there was evidence of nerve cell rewiring. The benefits also lasted, with follow-up periods of up to three years in this study.
We now know that new neuronal connections can be established in the retina; There are many other related avenues of research to explore, including the role of calcium signaling (which CaBP4 manages) in managing cellular communication in the eye.
We’ve seen encouraging advances in treatments to restore vision in recent years, including activating dormant cells in the eye and protecting photoreceptors, and this is another item to add to the list.
“Our results show a restoration of visual function in dogs with severe electrophysiological and synaptic dysfunction,” the researchers write.
“We establish that the retinal OPL has profound plasticity and that synaptic ribbons can mature and elongate after gene augmentation therapy into adulthood.”
The research was published in Advances in molecular therapy.
This article was fact-checked by Fiona MacDonald and edited by Fiona MacDonald. Although we are proud of our process, we are only human. If you spot an error, please let us know.
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