Researchers have used mice with nine different genetic backgrounds to identify factors influencing eye ageing, paving the way for eye-based diagnostics for neurodegenerative diseases.
The research, from The Jackson Laboratory (JAX), an independent global nonprofit biomedical research institution, examined age-related changes in genes and proteins of the retinas of nine strains of mice, mimicking the genetic variability found in humans.
Traditionally, studies of retinal ageing and disease have relied on a single strain of genetically identical mice, limiting researchers’ ability to understand the role of genetic variation.
“The challenge in studying age-related eye diseases is that ageing is heterogeneous,” said Professor Gareth Howell, the Diana Davis Spencer Foundation Chair for Glaucoma Research at JAX, who led the research.1
“Observing how ageing occurs in one strain of mice might not be relevant to all mice – or humans.”
One of the most significant discoveries in the study was the identification of two mouse strains that closely resemble human retinal diseases.
By performing eye exams – similar to those undertaken by humans – the team found the Watkins Star Line B (WSB) strain of mice developed characteristics of age-related macular degeneration and retinitis pigmentosa. The New Zealand Obese (NZO) strain, known for its severe obesity and diabetes, developed diabetic retinopathy.
Gene and protein analysis in both strains of mice predicted that they would develop common age-related eye diseases.
“It was promising to see that the molecular data we generated predicted specific retinal cell abnormalities in these two strains,” said Olivia Marola, a co-first author of the paper.
“When we saw unique changes in NZO’s retinal ganglion cells at the molecular level, sure enough, we saw drastic functional changes in those cells.”
These models will allow researchers to study how these diseases progress and explore potential treatments. It could also help other scientists choose which mouse models to use in their own ageing-related work or carry out further studies to pinpoint individual genes that are associated with accelerated eye ageing and eye disease such as cataracts, glaucoma, macular degeneration, and diabetic retinopathy.
Beyond vision research, this study could have broader implications for neurodegenerative diseases like Alzheimer’s and other forms of dementia.
“The eye is a crucial organ, and this research fills an important gap in our understanding of ageing,” said Prof 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.”
The research was published in Molecular Neurodegeneration.2
References available at mivision.com.au.