This just in—Our bodies change as we age. Okay, you already knew that fact. Still, age-related changes happen in different ways, depending on many factors. When it comes to vision, some people experience age-related vision decline more severely than others, and these declines can lead to degenerative diseases such as cataract formation and age-related macular degeneration. Research is exploring these issues—read on to find out what scientists have learned.
Different Genetics, Different Outcomes
Scientists at The Jackson Laboratory demonstrated that genetics plays an important role in how the eye ages—specifically, how different genetic backgrounds influence retinal aging. This study looked at nine strains of mice, rather than just one. Studying only one strain had previously limited researchers’ ability to understand how genetic variation works. By studying different strains, researchers were better able to reflect human genetic diversity. From these mice, they collected data on age-related changes in both young and old mice.
One discovery that was telling was the identification of two mouse strains that resemble human retinal diseases. Researchers found that the Watkins Star Line B (WSB) strain developed characteristics of age-related macular degeneration and retinitis pigmentosa. Another strain, known as the New Zealand Obese (NZO) strain, is responsible for severe obesity and diabetes, and diabetic retinopathy. Gene and protein analysis of both strains predicted that they would develop age-related eye diseases.
These models will help scientists study how age-related eye diseases develop and may lead to potential treatments. They can also help researchers choose the most appropriate mouse models for identifying specific genes associated with cataracts, glaucoma, macular degeneration, and diabetic retinopathy.
Novel Way to Treat Degenerative Diseases
Many times when something breaks, you can replace a worn-out part with a new one and the item is as good as new. Wouldn’t it be nice if that could be done at the cellular level? Scientists at Florida Atlantic University (FAU) Schmidt College of Medicine think so, They received a five-year $1.9 million grant from the National Eye Institute of the National Institutes of Health for work involved in treating degenerative diseases by replacing malfunctioning cells with new, healthy cells.
Replacement cells can be genetically engineered in a lab by programming of embryonic stem cells. While there are multiple ways to program the stem cells into adult cells, a big problem has been identifying the mechanisms that drive adult cell development.
That’s where this grant comes in. Researchers are working to understand the novel mechanisms that turn immature eye lens precursor cells into functional transparent cells. One important discovery is that low oxygen is a driver of cellular reprograming events that that create mature transparent lens cells. What they want to find out are the ways of controlling this low oxygen induced cellular transformation event.
When it comes to the eye lens, the progress of how immature cells develop into the mature form, involves a single layer of epithelial cells on the surface that change into fiber cells. For fiber cells to mature and make a clear lens, they must activate specific genes responsible for structural proteins known as crystallins. They must also undergo metabolic changes, such as switching to glycolysis and removing internal organelles. If this fails, it can lead to cataracts. The work at FAU Schmidt College of Medicine focuses on how low oxygen conditions in the lens core can drive gene activation through specialized transcriptional and epigenetic mechanisms.
Scientists are focusing on learning more about the molecular and mitochondrial mechanisms that drive ocular development and disease. They do this through the use of eye lens and retina as models to explore cellular differentiation, function and disease processes. The goal is to use the insights from this work to engineer cell systems and transplantable cells that can restore the function of damaged organs.
One day diseases, like age-related macular degeneration, glaucoma and diabetic retinopathy, may no longer inevitably lead to vision loss. Research projects at The Jackson Laboratory and Florida Atlantic University are advancing our understanding of the genetic factors that lead to eye disease and are paving the way for new stem cell–based treatments. Thanks to their work, future patients may benefit from therapies that restore vision, rather than merely preserve what’s left.
https://www.fau.edu/newsdesk/articles/nih-grant-degenerative-disease