Blocking the PROX1 protein allowed KAIST researchers to regenerate broken retinas and restore imaginative and prescient in mice.
Imaginative and prescient is likely one of the most vital human senses, but greater than 300 million folks around the globe are susceptible to dropping it as a consequence of varied retinal ailments. Though latest remedies have helped sluggish the development of those circumstances, no efficient remedy has been in a position to restore imaginative and prescient that has already been misplaced, till now. Researchers at KAIST have developed a brand new drug that efficiently restores imaginative and prescient.
On March 30, KAIST introduced {that a} analysis group headed by Professor Jin Woo Kim from the Division of Organic Sciences has created a remedy that regenerates retinal nerves to revive imaginative and prescient.
In experiments utilizing a disease-model mouse, the group achieved each retinal regeneration and imaginative and prescient restoration by blocking the PROX1 (prospero homeobox 1) protein, which usually prevents retinal restore. The outcomes had been long-lasting, with results persevering with for greater than six months.
First long-term retinal restore in mammals
This research marks the primary profitable induction of long-term neural regeneration in mammalian retinas, providing new hope to sufferers with degenerative retinal ailments who beforehand had no remedy choices.
As the worldwide inhabitants continues to age, the variety of retinal illness sufferers is steadily growing. Nonetheless, no remedies exist to revive broken retinas and imaginative and prescient. The first cause for that is the mammalian retina’s incapability to regenerate as soon as broken.
Research on cold-blooded animals, akin to fish—identified for his or her strong retinal regeneration—have proven that retinal accidents set off Müller glia cells to dedifferentiate into retinal progenitor cells, which then generate new neurons. Nonetheless, in mammals, this course of is impaired, resulting in everlasting retinal harm.
PROX1 protein recognized as a regeneration blocker
Via this research, the analysis group recognized the PROX1 protein as a key inhibitor of Müller glia dedifferentiation in mammals. PROX1 is a protein present in neurons of the retina, hippocampus, and spinal twine, the place it suppresses neural stem cell proliferation and promotes differentiation into neurons.
The researchers found that PROX1 accumulates in broken mouse retinal Müller glia, however is absent within the extremely regenerative Müller glia of fish. Moreover, they demonstrated that the PROX1 present in Müller glia shouldn’t be synthesized internally however fairly taken up from surrounding neurons, which fail to degrade and as an alternative secrete the protein.
Based mostly on this discovering, the group developed a way to revive Müller glia’s regenerative capability by eliminating extracellular PROX1 earlier than it reaches these cells.
This strategy includes utilizing an antibody that binds to PROX1, developed by Celliaz Inc., a biotech startup based by Professor Jin Woo Kim’s analysis lab. When administered to disease-model mouse retinas, this antibody considerably promoted neural regeneration. Moreover, when delivered, the antibody gene to the retinas of retinitis pigmentosa illness mannequin mice, it enabled sustained retinal regeneration and imaginative and prescient restoration for over six months.
The retinal regeneration-inducing remedy is at present being developed by Celliaz Inc. for software in varied degenerative retinal ailments that at present lack efficient remedies. The corporate goals to start medical trials by 2028.
Dr. Eun Jung Lee said, “We’re about to finish the optimization of the PROX1-neutralizing antibody (CLZ001) and transfer to preclinical research earlier than administering it to retinal illness sufferers. Our purpose is to supply an answer for sufferers susceptible to blindness who at present lack correct remedy choices.”
Reference: “Restoration of retinal regenerative potential of Müller glia by disrupting intercellular Prox1 switch” by Eun Jung Lee, Museong Kim, Sooyeon Park, Ji Hyeon Shim, Hyun-Ju Cho, Jung Ah Park, Kihyun Park, Dongeun Lee, Jeong Hwan Kim, Haeun Jeong, Fumio Matsuzaki, Seon-Younger Kim, Jaehoon Kim, Hanseul Yang, Jeong-Soo Lee and Jin Woo Kim, 25 March 2025, Nature Communications.
DOI: 10.1038/s41467-025-58290-8
This analysis was supported by analysis funds from the Korean Nationwide Analysis Basis (NRF) and the Korea Drug Improvement Basis (KDDF).
