Researchers at the Korea Advanced Institute of Science and Technology (KAIST) have achieved a significant breakthrough in treating retinitis pigmentosa, developing an antibody treatment that successfully restored vision in mice for over six months. The innovative approach targets a key protein that prevents natural retinal regeneration in mammals, offering new hope for treating the leading cause of inherited blindness.
Targeting the Root of Retinal Degeneration
Retinitis pigmentosa affects approximately 1.5 million people worldwide and represents the number one cause of inherited retinal degeneration-associated blindness. The disease causes the breakdown of light-sensitive photoreceptor cells in the retina, leading to progressively declining vision and eventual loss of central vision. Currently, no known cure exists for this condition.
The KAIST research team drew inspiration from zebrafish, which possess the remarkable ability to regenerate damaged retinal cells. When fish suffer retinal damage, specialized cells called Müller glia cells differentiate into retinal progenitor cells, generating new neurons and maintaining proper vision function. These Müller glia cells form a coating that connects the inner and outer layers of the retina, help remove neuronal waste from the eye, and assist with light transmission.
Identifying the Mammalian Barrier
Through studies of donated human eyes and engineered mouse models with retinal damage, the researchers identified why mammals lack this regenerative capability. They discovered that a protein called PROX1, present in damaged human and mouse eyes, inhibits Müller glia cells from differentiating in mammals. With this differentiation blocked, the glia cells cannot regenerate retinal cells naturally.
Breakthrough Antibody Treatment
The research team developed a targeted antibody that binds to PROX1, effectively blocking its inhibitory action. When this antibody was injected into the retinas of mice with retinitis pigmentosa, the treatment successfully restored retinal regeneration and returned vision for a period exceeding six months.
"We are about completing the optimization of the PROX1-neutralizing antibody (CLZ001) and move to preclinical studies before administering it to retinal disease patients," said first study author Eun Jung Lee. "Our goal is to provide a solution for patients at risk of blindness who currently lack proper treatment options."
Path to Human Clinical Trials
The team is advancing the PROX1 antibody development through KAIST spinout company Cellia Inc., with plans to initiate human trials in 2028. The treatment is being developed not only for retinitis pigmentosa but also for other retinal diseases that currently lack cures.
The research represents a paradigm shift in treating inherited blindness by harnessing the body's natural regenerative mechanisms rather than relying on external devices or genetic modifications. By removing the molecular brake that prevents retinal regeneration in mammals, this approach could potentially restore vision to millions of patients worldwide who face progressive vision loss from retinal degenerative diseases.
The findings have been published in Nature Communications, marking a significant advancement in regenerative ophthalmology and offering tangible hope for patients with previously untreatable forms of inherited blindness.
