Vision is one of the most crucial human senses, yet over 300 million people worldwide are at risk of vision loss due to various retinal diseases. While recent advancements in retinal disease treatments have successfully slowed disease progression, no effective therapy has been developed to restore already lost vision—until now. KAIST researchers have successfully developed a novel drug to restore vision.
< Photo 1. (From left) Ph.D. candidate Museong Kim, Professor Jinwoo Kim, and Dr. Eun Jung Lee of KAIST Department of Biological Sciences >
KAIST (represented by President Kwang Hyung Lee) announced on the 30th of March that a research team led by Professor Jinwoo Kim from the Department of Biological Sciences has developed a treatment method that restores vision through retinal nerve regeneration.
The research team successfully induced neural regeneration and vision recovery in a disease-model mouse by administering a compound that blocks the PROX1 (Prospero Homeobox 1) protein, which suppresses retinal regeneration. Furthermore, the effect lasted for more than six months.
This study marks the world's first successful induction of long-term neural regeneration in mammalian retinas, offering new hope to patients with degenerative retinal diseases who previously had no treatment options.
As the global population continues to age, the number of retinal disease patients is steadily increasing. However, no treatments exist to restore damaged retinas and vision. The primary reason for this is the mammalian retina's inability to regenerate once damaged.
Studies on cold-blooded animals, such as fish—known for their robust retinal regeneration—have shown that retinal injuries trigger Müller glia cells to dedifferentiate into neural progenitor cells, which then generate new neurons. However, in mammals, this function is lost, leading to permanent retinal damage.
< Figure 1. Schematic diagram of the mechanism of retinal regeneration through inhibition of PROX1 migration. PROX1 protein secreted from damaged retinal nerve cells migrates to Müllerglia and inhibits dedifferentiation into neural progenitor cells and neural regeneration. When PROX1 is captured outside the cells with a neutralizing antibody against PROX1 and its migration to Müllerglia is inhibited, dedifferentiation of Müllerglia cells and neural cell regeneration processes are resumed, restoring retinal function. >
Through this study, the research team identified the PROX1 protein as a key inhibitor of Müller glia dedifferentiation in mammals. PROX1 is a protein found in neurons of the retina, hippocampus, and spinal cord, where it suppresses neural stem cell proliferation and promotes differentiation into neurons.
The researchers discovered that PROX1 accumulates in damaged mouse retinal Müller glia, but is absent in the highly regenerative Müller glia of fish. Furthermore, they demonstrated that the PROX1 found in Müller glia is not synthesized internally but rather taken up from surrounding neurons, which fail to degrade and instead secrete the protein.
Based on this finding, the team developed a method to restore Müller glia's regenerative ability by eliminating extracellular PROX1 before it reaches these cells.
< Figure 2. Retinal regeneration and visual recovery in a retinitis pigmentosa model mouse through administration of AAV2-Anti-PROX1 gene therapy. We demonstrate that after administration of adeno-associated virus (AAV2-Anti-PROX1) expressing PROX1 neutralizing antibodies to the eyes of RP1 retinitis pigmentosa model mice with vision loss, the photoreceptor cell layer of the retina is restored (A) and vision is restored (B). >
This approach involves using an antibody that binds to PROX1, discovered by Celliaz Inc., a biotech startup founded by Professor Jinwoo Kim's research lab. This PROX1-neutralizing antibody exhibited superior binding affinity compared to existing antibodies. When administered to disease-model mouse retinas, this antibody significantly promoted neural regeneration. Additionally, when delivered as a type of gene therapy in mice with congenital retinal degeneration, it enabled sustained neuronal production and vision restoration for over six months.
The retinal regeneration-inducing therapy is currently being developed by Celliaz Inc. for application in various degenerative retinal diseases that currently lack effective treatments. The company aims to begin clinical trials by 2028.
This study was co-authored by Dr. Eun Jung Lee of Celliaz Inc. and Museong Kim, a Ph.D. candidate at KAIST, as joint first authors. The findings were published online on March 26 in the international journal Nature Communications. (Paper Title: Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 transfer | DOI: 10.1038/s41467-025-58290-8)
Dr. Eun Jung Lee stated, "We are finalizing improvements to the efficacy of the PROX1-neutralizing antibody (CLZ001) and aim to complete vision restoration efficacy and safety evaluations in multiple animal models before administering it to retinal disease patients. Our goal is to provide a real solution for patients at risk of blindness who currently lack proper treatment options."
This research was supported by the National Research Foundation of Korea's Mid-Career Researcher Support Program and the National New Drug Development Project.
