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Subspecialties Retina, Basic & Translational Research

Sowing the Stem Cells

Photoreceptor degeneration occurs in various types of inherited retinal diseases and, when left untreated, can eventually lead to long-term vision loss and blindness in patients suffering from genetically-linked diseases, such as retinitis pigmentosa and age-related macular degeneration. Looking at ways to combat this currently untreatable and irreversible photoreceptor degeneration, an international preclinical study conducted by Duke-NUS Medical School (US), the Singapore Eye Research Institute (Singapore), and the Karolinska Institutet (Sweden) (1), has developed a novel stem cell technique that produces photoreceptor progenitor cells closely resembling those found in the human retina. 

“I saw an unmet clinical need for blindness caused by loss of photoreceptors in patients in advanced stages of inherited retinal diseases and age-related macular degeneration,” explains Tay Hwee Goon, lead author of the study and associate professor at the Centre for Vision Research, Duke-NUS Medical School. “There is no effective treatment for these diseases, and replacement of functional photoreceptors appeared to be the most promising route towards retina regeneration with the prospect of vision restoration.” 

Transplanting these photoreceptor progenitor cells into the damaged retinas of rodents, the researchers were excited to discover that “the cells began to express markers similar to those of mature photoreceptors.” There were some obstacles to the transplantation procedure, however. Goon cites challenges around selecting a suitable genetic rodent model that mimicked patients with inherited retinal diseases, optimizing timepoints, immunosuppression, and cell dose for cell transplantation. He explains, “We are currently performing extensive experiments to study and address the above issues in large eye preclinical models that are most physiologically similar to the human eye.”.

In order to gauge vision improvements in their rodent subjects, the study employed the water maze swimming test, as well as an electroretinogram, to identify any recovery to the damaged retinas. The preclinical models indicated a notable improvement in vision, with the transplanted cells establishing connections with cells and nerves in the inner retina and continuing to function effectively for many weeks. “We found that these cells could slow down vision loss after two weeks and improve retina function after four weeks of transplantation,” notes Goon. 

The novel protocol has now been licensed to Alder Therapeutics, which will “focus on the quality control in the manufacturing of photoreceptor progenitors, but at a clinical grade level,” says Goon. “These cells will subsequently be tested for safety and efficacy extensively within five years before advancing to the next stage. By the end of this period, our lab hopes to see vision being restored in patients with vision loss and improve their quality of life.”

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  1. TH Goon et al., “Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function,” Molecular Therapy, 31, 825 (2023). PMID: 36638800.
About the Author
Alun Evans

Coming from a creative writing background, I have a great interest in fusing original, narrative-driven concepts with informative, educational content. Working at The Ophthalmologist allows me to connect with the great minds working in the field of contemporary eye care, and explore the human element involved in their scientific breakthroughs.

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