New research from The Jackson Laboratory (JAX) has shed light on the genetic factors that influence the aging of the eye, particularly how certain individuals may be more susceptible to age-related eye diseases. The study, published in Molecular Neurodegeneration, emphasizes the role genetics play in retinal aging, revealing that different genetic backgrounds can significantly affect how the eye deteriorates with age.
The study examined the genetic and molecular changes in the retinas of nine different strains of mice, chosen to reflect the genetic diversity seen in humans. While all the mice displayed typical signs of aging, the severity and type of retinal degeneration varied greatly across the different strains, providing new insights into the genetic underpinnings of age-related vision loss.
A More Accurate Model for Eye Aging
Traditionally, research on retinal aging has been conducted using a single strain of genetically identical mice. This approach, while useful, has its limitations in reflecting the genetic variation that exists in humans. According to Gareth Howell, professor and chair of Glaucoma Research at JAX, the challenge in studying age-related eye diseases lies in their heterogeneity. “Aging does not affect all individuals in the same way, and studying just one strain of mice may not be relevant to all humans,” he said.
By leveraging a more diverse set of mouse strains with varying genetic backgrounds, Howell and his team were able to gain a deeper understanding of how genetic context drives retinal aging. Their work, which now features publicly available data, aims to help other researchers studying aging and vision loss. This research could potentially improve our ability to use the eye as a biomarker for brain health, offering a window into neurological conditions like Alzheimer’s disease.
Genetic and Protein Findings Predict Retinal Diseases
Among the key findings of the study were the identification of two mouse strains that closely resemble common human retinal diseases. The Watkins Star Line B (WSB) strain exhibited symptoms akin to age-related macular degeneration and retinitis pigmentosa, a rare inherited condition that leads to blindness. Meanwhile, the New Zealand Obese (NZO) strain, which is prone to obesity and diabetes, developed diabetic retinopathy.
The researchers used eye exams similar to routine optometrist tests to detect these conditions, and their genetic and protein analysis predicted these age-related eye diseases in both mouse strains. Olivia Marola, a postdoctoral associate at JAX and co-first author of the study, highlighted the significance of these findings. “It was promising to see that the molecular data we generated predicted specific retinal cell abnormalities in these two strains,” she said.
These discoveries could aid researchers in studying the progression of these diseases and testing potential treatments. Additionally, the models used in the study can help other scientists choose the most appropriate mouse models for their own research into aging and vision-related diseases, such as cataracts, glaucoma, macular degeneration, and diabetic retinopathy.
The Retina as a Window into Neurological Decline
Beyond its implications for vision research, the study also carries potential significance for neurodegenerative diseases. Since the retina is a direct extension of the brain, understanding its aging process could provide valuable clues about conditions like Alzheimer’s disease and other forms of dementia.
“The eye is a crucial organ, and this research fills an important gap in our understanding of aging,” said Howell. “But beyond that, the eye is a window into the brain. 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.”
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