Stem Cell Therapy Could Restore Vision to Those With Macular Degeneration and Other Blinding Eye Diseases

Summary: A new method enables the production of photoreceptor progenitor cells that resemble embryonic cells. These cells can be transplanted and restore retinal function, and ultimately recovery of vision for those with blinding diseases including age-related macular degeneration and retinitis pigmentosa.

Source: Duke-NUS Medical School

A preclinical study using stem cells to produce progenitor photoreceptor cells—light-detecting cells found in the eye—and then transplanting these into experimental models of damaged retinas has resulted in significant vision recovery.

This finding, by scientists at Duke-NUS Medical School, the Singapore Eye Research Institute and the Karolinska Institute in Sweden, marks a first step toward potentially restoring vision in eye diseases characterized by photoreceptor loss.

The research is published in the journal Molecular Therapy.

“Our laboratory has developed a novel method that enables the production of photoreceptor progenitor cells resembling those in human embryos,” said Assistant Professor Tay Hwee Goon, first author of the study from Duke-NUS’ Center for Vision Research.

“Transplantation of these cells into experimental models has yielded partial restoration of the retinal function.”

The degeneration of photoreceptors in the eye is a significant cause of declining vision that can eventually lead to blindness and for which there is currently no effective treatment.

Photoreceptor degeneration occurs in a variety of inherited retinal diseases, such as retinitis pigmentosa—a rare eye disease that breaks down cells in the retina over time and eventually causes vision loss—and age-related macular degeneration, a leading cause of vision impairment worldwide.

Tay and her team developed a procedure to grow human embryonic stem cells in the presence of purified laminin proteins that are involved in normal development of human retinas. In the presence of the laminins, stem cells could be directed to differentiate into photoreceptor progenitor cells responsible for converting light into signals that are sent to the brain.

When these cells were transplanted into damaged retinas, the preclinical models showed significant recovery of vision. A diagnostic test called electroretinogram also identified significant recovery in the retinas via electrical activity in the retina in response to a light stimulus.

The transplanted cells established connections with surrounding retinal cells and nerves in the inner retina. They also survived and functioned for many weeks after transplantation.

Moving forward, the team hopes to refine their method to make it simpler and achieve more consistent results than earlier attempts to explore stem cell therapy for photoreceptor cell replacement.

This shows an eye
The degeneration of photoreceptors in the eye is a significant cause of declining vision that can eventually lead to blindness and for which there is currently no effective treatment. Image is in the public domain

“It is exciting to find these results, which suggest a promising route towards using stem cells to treat those forms of visual deterioration and blindness caused by the loss of photoreceptors,” said Dr. Helder Andre, Head of Molecular and Cellular Research from Karolinska Institute’s Department of Clinical Neuroscience and a senior author of the study.

Associate Professor Enrico Petretto, Director of the Center for Computational Biology at Duke-NUS and the study’s bioinformatics analysis lead, added, “Our method may also be useful for understanding the molecular and cellular pathways that drive the progression of macular degeneration, perhaps leading to the development of other therapeutic approaches.”

The next challenge for the researchers is to explore the efficacy of their method in models of photoreceptor degeneration that more closely match the human condition.

“If we get promising results in our future studies, we hope to move to clinical trials in patients,” said Professor Karl Tryggvason, from Duke-NUS’ Cardiovascular and Metabolic Disorders Program, and the corresponding author of the study. “That would be an important step towards for being able to reverse damage of the retina and restore vision.”

The protocol underlying the procedure developed by Tay has since been licensed to Swedish biotech start-up Alder Therapeutics.

About this genetics and visual neuroscience research news

Author: Press Office
Source: Duke-NUS Medical School
Contact: Press Office – Duke-NUS Medical School
Image: The image is in the public domain

Original Research: Open access.
Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function” by Hwee Goon Tay et al. Molecular Therapy


Photoreceptor laminin drives differentiation of human pluripotent stem cells to photoreceptor progenitors that partially restore retina function

Blindness caused by advanced stages of inherited retinal diseases and age-related macular degeneration are characterized by photoreceptor loss. Cell therapy involving replacement with functional photoreceptor-like cells generated from human pluripotent stem cells holds great promise.

Here, we generated a human recombinant retina-specific laminin isoform, LN523, and demonstrated the role in promoting the differentiation of human embryonic stem cells into photoreceptor progenitors. This chemically defined and xenogen-free method enables reproducible production of photoreceptor progenitors within 32 days.

We observed that the transplantation into rd10 mice were able to protect the host photoreceptor outer nuclear layer (ONL) up to 2 weeks post transplantation as measured by full-field electroretinogram. At 4 weeks post transplantation, the engrafted cells were found to survive, mature, and associate with the host’s rod bipolar cells.

Visual behavioral assessment using the water maze swimming test demonstrated visual improvement in the cell-transplanted rodents. At 20 weeks post transplantation, the maturing engrafted cells were able to replace the loss of host ONL by extensive association with host bipolar cells and synapses. Post-transplanted rabbit model also provided congruent evidence for synaptic connectivity with the degenerated host retina.

The results may pave the way for the development of stem cell-based therapeutics for retina degeneration.

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