When the tires on your car wear out, some cars will show this by way of a specific light or message on the dashboard. When your kitchen knives get dull, you know this by the fact that you can’t slice things as easily. So, you either replace the tires or you renew the knives by sharpening them. What about our bodies, specifically our eyes? Is there a way to find out at the early on when cellular mechanisms become worn out and can that information be used to treat eye diseases? Well, here is what research has to say on the subject.
Replacing Damaged Cells with New Cells
Researchers in the lab of Mark Kantorow Ph.D., associate dean of graduate programs and a professor of biomedical science at Florida Atlantic University received a five-year $1.9 million grant from the National Eye Institute of the National Institutes of Health (NIH) for a new way to treat degenerative diseases by replacing damaged cells with new cells.
His lab learned that low oxygen (hypoxia) levels are responsible for cellular reprograming that then leads to the formation of mature transparent lens cells. This grant will help to identify the pathways running this hypoxia-induced cellular transformation event. New replacement cells can be made in the lab through the programming of embryonic stem cells. While many strategies have been developed to program the stem cells into functional adult cells, an obstacle has been identifying all the requirements for adult cell formation. This grant will help to ascertain the mechanisms that turn immature eye lens precursor cells into functional transparent cells.
Their work will look at the role played by hypoxia-inducible transcription factor 1 or HIF1a in control of lens gene expression. They will also study the requirement for oxygen-induced gene-expression that led to modifications in the regulation of the DNA structure. This study plans to use the lens cells as a model to look for clues into the development of ways to engineer complex cells and tissues, leading to the development of therapies for the treatment of degenerative disease.
Speaking of the eye’s lens, how the immature cells develop into the mature form involves a single layer of epithelial cells on the surface that transform into fiber cells. For the fiber cells to mature and make the lens clear, they have to trigger specific genes responsible for structural proteins, such as crystallins, metabolic changes, and the removal of internal organelles. If this fails, it can lead to cataracts.
Scientists will analyze the role of genes associated with ocular disease to study the effects of environmental factors like UV light and other things that affect mitochondrial and cellular functions. They will also look at how key cellular systems can be engineered to either prevent or treat conditions, like cataracts and macular degeneration. The goal is to use these insights to create cell systems and transplantable cells that can restore the function of damaged tissues and organs.
New Way to Look at an Old Marker
Annexin-V has been used as a marker of cell death in retinal ganglion cells. Damage to these neurons is what leads to vision loss in glaucoma. Findings from a National Eye Institute-led study provides new information on how annexin-V can be interpreted both in the lab and clinic for tracking retinal cell death in diseases, like glaucoma.
It was discovered that annexin-V binds to immune cells, which can complicate the interpretation when using this biomarker. Annexin-V becomes a marker of cell death because it binds with to phosphatidyl serine, a lipid that moves to the surface of a cell in the early stages of programmed cell death, known as apoptosis. Annexin-V also appears at the optic nerve head, which doesn’t have retinal ganglion cell somas (the main part of the neuron). This region is the point where axons from the retinal ganglion cells leave the eye and form the optic nerve that goes into the brain.
So, the researchers used an optic nerve crush model to validate this discovery. This model is well established since there is a firm understanding of retinal cell death, namely when the retinal ganglion cells are damaged, it leads to apoptosis not necrosis. What they found is that annexin-V binds to both retinal ganglion cell that are going through apoptosis, and to immune cells and a subset of microglial cells in the retina. This suggests that annexin-V has a role to play in detecting early inflammatory responses. Microglia cells are the first to respond to damage and changes in their environment.
Since annexin-V binds to retinal immune cells in response to injury or disease, this can lead to opportunities to monitor potential therapeutic targeting of microglial activation and neuro-inflammation of the retina. This can be utilized to study possible treatment for diseases such as glaucoma, age-related macular degeneration, and retinitis pigmentosa.
While it is safe to assume that in the next few month, there won’t be clinics where you can get an injection of stem cell or find out if annexin-V is active, research studying these items are showing promise. Thanks to the work of scientists at Florida Atlantic University and the National Eye Institute, one day it will be possible to renew cellular mechanisms so that vision doesn’t deteriorate as a result of eye disease.
Sources:
https://www.fau.edu/newsdesk/articles/nih-grant-degenerative-disease
https://www.nei.nih.gov/about/news-and-events/news/nei-study-new-take-old-marker-cell-death