A research team of the Korea Advanced Institute of Science & Technology (KAIST) has developed the world’s first retinal disease treatment that can restore damaged vision.
KAIST announced on March 30 that Prof. Kim Jin-woo’s team from the Department of Biological Sciences has developed a treatment method that can restore vision through retinal nerve regeneration.
The team successfully induced neural regeneration and vision recovery in retinal tissue by administering a substance that blocks the “Prox1” protein, which inhibits retinal regeneration, into the eyes of disease model mice. The effects lasted for more than six months.
This is the first case in the world to induce long-term neural regeneration in mammalian retinas and is expected to bring hope to patients with degenerative retinal diseases, for which no treatment currently exists.
There is currently no treatment to restore the retina and vision of patients with damage.
Research on ectothermic animals like fish, which have active retinal regeneration, shows that fish have the ability to generate new nerve cells by dedifferentiating Müller glia cells in the retina into neural progenitor cells when retinal damage occurs. However, in mammals like humans, this function is lost, resulting in permanent damage as retinal regeneration does not occur.
In this study, Prof. Kim’s team identified the Prox1 protein as a factor that inhibits the dedifferentiation of mammalian Müller glia cells. Prox1 is a protein generated in the nerve cells of neural tissues such as the retina, hippocampus, and spinal cord, which suppresses the division of neural stem cells and induces differentiation into nerve cells.
The research team discovered that the Prox1 protein accumulates in the Müller glia of damaged mouse retinas but not in the Müller glia of fish, where regeneration is active.
They also identified that the Prox1 in Müller glia is not internally generated but is secreted by surrounding nerve cells that fail to degrade it, which is then taken up by Müller glia.
The research team developed a method to restore the neural regeneration ability of Müller glia by removing Prox1 secreted from nerve cells externally before it reaches Müller glia.
The research team explained, “The PROX1 protein secreted from damaged retinal nerve cells moves to Müller glia, inhibiting dedifferentiation into neural progenitor cells and neural regeneration. By capturing external PROX1 with a neutralizing antibody against PROX1, we can prevent its movement to Müller glia, restart the dedifferentiation and neural regeneration process of Müller glia cells, and restore retinal function.”
This method utilizes antibodies that bind to Prox1, discovered by Celliaz Inc., a startup founded by Prof. Kim as a lab venture (a KAIST faculty startup).
In particular, it was proven that when the Prox1 neutralizing antibody was administered to disease-modeling mouse retinas, active neural regeneration occurred, and when delivered in the form of a gene therapy to congenital retinal degenerative disease mouse retinas, continuous generation of nerve cells and vision recovery were maintained for over six months.
Celliaz is currently developing a retinal regeneration-inducing treatment based on these research results to apply to various degenerative retinal diseases, with the goal of entering clinical trials by 2028.
This research, with Dr. Lee Eun-jeong from Celliaz and KAIST doctoral student Kim Moo-sung as co-first authors, was published online in the international journal “Nature Communications” on March 26 (Paper title: Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer).
Dr. Lee stated, “The work to improve the efficacy of the Prox1 neutralizing antibody is complete, and after evaluating its vision restoration efficacy and safety using various animals, we will proceed with administration to retinal disease patients,” adding, “We will strive to make a practical contribution to patients at risk of blindness without appropriate treatment.”
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