Aging not only leads to changes in our bodies, it also leads to diseases, such cancer, neurodegenerative diseases and vision diseases. When it comes to the eye and vision, why are some people more likely to developing eye diseases than others? When it comes to neurodegenerative diseases, can the eye be utilized as an early warning system, as it is for diabetes and high blood pressure? Research at The Jackson Laboratory and University of Alabama Birmingham are working to find the answers to these questions.
Work done at The Jackson Laboratory in the lab of Gareth Howell, PhD, professor and Diana Davis Spencer Foundation Chair for Glaucoma Research found that genetics plays in important role in how the eye ages. This study looked at age-related changes in the genes and proteins in nine strains of mice. Previous studies of retinal aging and disease looked at a single strain of mice and this limited scientists’ ability to understand the role of genetic variation.
Researchers studied these mice with different genetic backgrounds and were able to generate data on age-related genetic and molecular changes in young and old mice. The data is publicly available here: https://thejacksonlaboratory.shinyapps.io/Howell_AgingRetinaOmics/
A noteworthy discovery in this study was the identification of two mouse strains that resemble human retinal diseases. They examined the mice eyes and found that the Watkins Star Line B (WSB) strain developed characteristics of age-related macular degeneration and retinitis pigmentosa and the New Zealand Obese (NZO) developed diabetic retinopathy. They also found that gene and protein analysis in both of these strains predicted that they would develop age-related eye disease. These models can help scientists both learn how these diseases progress and eventually, develop treatments.
This research also provided insights into the use of the retina as a biomarker for neurogenerative diseases, such as Alzheimer’s. Since the retina is an extension of the brain, learning how it ages can provide information about Alzheimer’s and other forms of dementia.
“[The] eye is a window into the brain,” said Howell. “By understanding how the healthy eye ages, we may be able to work toward new ways of using the eyes to determine people’s risk of developing diseases, like Alzheimer’s.”
Research at the University of Alabama Birmingham (UAB) found a possible biomarker for Alzheimer’s in the retina. Scientists in the lab of Edmund Arthur, OD, PhD, an assistant professor in the UAB School of Optometry, found a potential link between putative retinal gliosis and Alzheimer’s Disease.
Putative retinal gliosis occurs when the glial cells are activated when there is damage or disease in the retina. He found that presumed neuroinflammation was larger in the retinas of preclinical Alzheimer’s patients compared control subjects of the same age. (Preclinical Alzheimer’s patients are persons who aren’t cognitively impaired, but have elevated amyloid beta (Aβ) when viewed on positron emission tomography (PET) imaging.)
While mouse models of Alzheimer’s and autopsies of persons with Alzheimer’s showed retinal glial activation, this was the first time this was seen live in the retina of preclinical Alzheimer’s patients using imaging technology that is available in most eye clinics. Neuroinflammation usually comes before neurodegeneration and symptoms of dementia, and the retina provides a non-invasive way get an early diagnosis of the disease. So, this research was able to show it is possible to get this early diagnosis during the preclinical phrase using noninvasive and low-cost methods.
Next researchers plan to do a longitudinal study with a larger and more diverse population to see these changes over time and to see it association with plasma-based biomarkers. They also want to study the diagnostic value of a multimodal model of retinal gliosis and plasma-based biomarkers for detecting preclinical Alzheimer, as opposed to each biomarker on its own.
As research continues to uncover the connections between aging, genetics, and the eye, scientists are gaining a clearer view of how vision can reveal the broader story of our health. Studies like those at The Jackson Laboratory and the UAB are demonstrating not only why some individuals are more prone to eye disease, but also how the retina might serve as an early indicator of neurodegenerative conditions, like Alzheimer’s. By using the eye as both a model and a diagnostic tool, researchers hope to detect diseases earlier, develop more targeted treatments, and ultimately improve quality of life as we age. In many ways, the eye truly is a window—not just to the brain, but to the future of preventive medicine.