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Stem Cells, Protein & The Ways Research Are Learning More About Them

Posted by Ilena Di Toro | Posted on November 1, 2022

As always, research shines a light on the eye and vision. Case in point, wouldn’t it be nice if people experiencing vision diseases, like a retinal disorder or age-related macular degeneration could receive treatments that were derived from either stem-cells or from a specific protein and vision would improve. Well, we will spotlight stem-cell based therapy and how the lack of a protein can lead to age-related macular degeneration.

Stem Cells to Treat Retinal Diseases
While the concept of introducing retinal cells developed from stem cells to improve vision sounds easy, things haven’t worked out so great for researchers. Either the introduced cells would die or they wouldn’t integrate with the retina. Scientists from the University of Pennsylvania School of Veterinary Medicine, University of Wisconsin, Children’s Hospital of Philadelphia, and the National Institutes of Health’s National Eye Institute found that when they used a cocktail of immunosuppressive drugs when the photoreceptor cells were introduced into the retinas of dogs, the cells survived and began forming connections with other retinal cells.

While researchers at the University of Pennsylvania School of Veterinary Medicine were successful in producing gene therapies for conditions that have known genes, in most cases of inherited retinal degermation, a gene wasn’t identified. In other cases, the disease has progressed to the point where no photoreceptor cells remained intact enough for gene therapy.

In order to function, the photoreceptor cells must form connections with the cells of the inner retina in order to deliver the visual information. So, the goal of cell therapy is to recreate the layer of photoreceptor cells and have it integrate with the retina’s other cell type so that signals can go from one layer to the next. The researchers used stem cell-derived precursors of human photoreceptor cells that were labeled with fluorescent markers and injected them into the retinas of seven dogs with normal vision and three with a form of inherited retinal degeneration. The researchers used non-invasive imaging techniques to track the cells. They found that the cell uptake was better in animals with retinal degeneration than those with normal retinas.

The reason for that is obviously the normal retina is intact, so it serves as a physical barrier that prevents the introduced cells from connecting with the other retina cells. In the case of the dogs with retinal degeneration, the retina was more permeable, so the cells has better ability to move to the correct layer of the retina and work with the other neurons.

Protein, Good for Vision and Muscles
A study from the National Institutes of Health’s National Eye Institute found that a protein known as pigment epithelium-derived factor may lead to age-related changes in the retina. This protein protects retinal support cells and is known as the “youth” protein since it is plentiful in young retinas. Yet, this protein declines during aging and this study sought to learn what the loss of this protein does to the retina.

Previous work had shown that this protein protects retinal cells by preventing both the abnormal growth of blood vessels in the retina and damage to the cells. The retinal pigment epithelium, which nourishes photoreceptors and recycles parts of the photoreceptor cells, known as “outer segments” which are used up and the tips are shed each time the photoreceptor detects light. The retinal pigment epithelium cells produce and secrete the pigment epithelium-derived factor protein. The protein binds to its receptor, known as PEDF-R. The binding stimulates the PEDF-R to break down lipid molecules. The molecules are key components of the cell membranes that enclose the photoreceptor outer segments and other cellular compartments. This breakdown is an important part of the recycling process of the outer segments. While scientists knew that the protein levels dropped during the aging process, they didn’t know if the loss was causing or was correlated with age-related changes in the retina.

To learn more, scientists studied a mouse model that didn’t have the gene that created the pigment epithelium-derived factor protein. They looked at the cellular structure of the retina in the mouse model and found that the nuclei of the retinal pigment epithelium cells were enlarged and they turned on four genes associated with aging and the levels of the pigment epithelium-derived factor protein were below normal. Also, unprocessed lipids and other photoreceptors outer segment parts accumulated in the retinal pigment epithelium layer of the retina. All of this demonstrates that there is a feedback-loop involving the pigment epithelium-derived factor protein that maintains the levels of PEDF-R and the lipid metabolism in the retinal pigment epithelium.

This projects show that how aging affects vision and what happens when certain proteins aren’t present. Both show how scientists are learning more about what happens when things aren’t working in the eye and some possible cellular and genetic particulars that can be utilized as treatment options.


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