There is an army of dormant cells in our eyes that prefer to stay asleep. However, waking them up in patients living with degenerative retinal disease can prevent blindness.
Rupendra Brahambhatt Published: May 08, 2023 05:57 AM EST Link: https://interestingengineering.com/health/degenerative-retinal-disease-cure
Researchers at the Université de Montréal (UdeM) have proposed a novel treatment strategy that promises to restore vision in patients living with degenerative retinal disease, an inherited medical condition that gradually impairs a person’s ability to read text, sense colors, see objects that are placed sideways, and eventually makes them completely blind.
The researchers claim that, unlike the few existing treatment options that can slow down or prevent retinal degeneration in patients only at an early stage, their approach also works for patients who are at an advanced stage of the illness.
A recently published study sheds light on the proposed approach and raises hope for millions of people across the globe who suffer from degenerative retinal disease. Here is how it works:
Reclaiming vision loss caused by retinal degenerative disease
People who have degenerative retinal disease — the cone photoreceptor cells in their eyes that are responsible for color vision, light intensity perception, and visual sharpness undergo constant deterioration. So as time passes, the number of cone cells kept on decreasing and patients suffer vision loss.
When a patient reaches the advanced stage of this disease, his or her eyes lose most of the cone cells, and the person is close to becoming completely blind. No known treatment can restore the cone cells in patients at this stage. Interestingly, the UdeM team found a treatment that involves the activation of dormant glial cells in the retina to restore cone-cell activity. Generally, the main role of retinal glial cells is to render metabolic support to photoreceptors and neurons that make the eyes work. In fish, these cells can also regenerate the retina in case of damage, however, glial cells in mammals lack the power to do so.
The researchers discovered that there are certain genes that can make dormant glial cells work like cone-photoreceptors in mammals also, and these new cone cells can make up for the loss of original cone cells in the eyes.
"We have identified two genes that, when expressed in these dormant cells called Müller cells, can convert them into retinal neurons," said Camille Boudreau-Pinsonneault, first author of the study and a researcher at UdeM.
The genes are called transcription factors Ikzf1 and Ikzf4. The study authors also conducted an in vivo experiment on a mouse model in which they were able to turn Müller cells into cells resembling the properties of cone photoreceptors just by activating the Ikzf factors.
According to the researchers, these results are exciting and their approach could one day allow doctors to restore vision loss caused by retinal degenerative disease in humans.
“We may one day be able to take advantage of the cells that are normally present in the retina and stimulate them to regenerate retinal cells lost to pathological conditions and to restore vision," said Ajay David, co-author of the study.
The researchers are now planning to further improve their technique so that it could be safely implemented in patients living with retinal degenerative disease.
The study is published in the journal PNAS.
The sequential production of cell types during neural development is controlled by temporal identity transcription factors, and heterochronic expression of these factors in progenitors reprograms developmental potential and promotes the production of temporally inappropriate cell types. It remains unknown, however, whether temporal factors can reprogram terminally differentiated cells. Here, we report that the combined expression of early temporal identity factors Ikzf1 and Ikzf4, homologs of Drosophila hunchback (hb), can convert uninjured retinal glia into neuron-like cells. Furthermore, we show that Ikzf1/Ikzf4 can reprogram fibroblasts into induced neurons (iNs) by altering chromatin accessibility and enabling a neuronal gene expression program. This work uncovers the reprogramming ability of temporal identity factors, opening the door to cell therapy approaches for neurodegenerative diseases.