JAX researchers identify key genetic factors influencing eye aging in mice

Vision changes are an inevitable part of aging, but why are some more susceptible to age -related eye diseases and why do some individuals experience a more serious decline than others? New research by the Jackson Laboratory (Jax) reveals that genetics play a key role in the way the eye gets older, with different genetic backgrounds that influence retinal aging in various ways.

The study, published in Molecular neurodegenerationExamined age -related changes in genes and proteins of the retina of nine tribes of mice, so that the genetic variability in humans mimics. While all mice showed expected signs of aging, the severity and nature of these changes varied considerably between the nine tribes.

A more accurate approach to model eye aging

Traditionally, studies of retinal aging and disease are limited on a single tribe of genetically identical mice, which limits the ability of researchers to understand the role of genetic variation. “The challenge in studying age-related eye diseases is that aging is heterogeneous,” says Gareth Howell, Professor and Diana Davis Spencer Foundation chairman for glaucoma research at Jax, who led the research. “Observing how aging takes place in one tribe of mice may not be relevant to all mice – or people. To overcome the limitations of earlier studies, we wanted to know how genetic context stimulates aging of the retina.”

In his work Howell and his team used nine tribes of mice with different genetic backgrounds that are designed to better reflect human variability, to generate data about age -related genetic and molecular changes in young and old mice. With their dataset now publicly available, Howell and his team hope that their findings will help other scientists to study aging and loss of vision – work that can also improve the usefulness of the eye as a brain window to be neurological decline to predict.

Genetic and protein analyzes predict eye diseases

One of the most important discoveries in the study was the identification of two mouse tribes that resemble human retina diseases. By conducting eye investigations -as a person would undergo in a routine optometrist agreement, the researchers discovered that the Star Line B (WSB) tribe of Watkins developed the characteristics of age -related macular degeneration and retinitis pigmentosa, a rare inherited form of blindness While while the obese obescent (NZO) of new -Zeeland, known for its serious obesity and diabetes, developed diabetic retinopathy. In addition, gene and protein analysis predicted in both mouse tribes that they would develop common age-related eye diseases.

It was promising to see that the molecular data that we generated predicted specific retinal cell abnormalities in these two tribes. When we saw unique changes in the retinal ganglion cells of NZO at a molecular level, we saw yes, we saw drastic functional changes in those cells. “

Olivia Marola, a Jax-postdoctoral employee and co-first author of the new paper

These models will enable researchers to study how these diseases progress and explore potential treatments, explained Michael Maclean, a post-doctoral employee and co-first author of the work.

It could also help other scientists choose which mouse models they should use in their own aging or further studies to designate individual genes that are associated with accelerated eye aging and eye disorders such as cataract, glaucoma, macular degeneration and diabetic retinopathy.

Retina as a biomarker for Alzheimer’s

In addition to vision research, this study could have broader implications for neurodegenerative diseases. Since the retina is a direct expansion of the brain, it can understand how older can give indications about conditions such as Alzheimer’s and other forms of dementia.

“The eye is a crucial body and this research fills an important gap in our understanding of aging,” said Howell. “But otherwise the eye is a window in the brain. By understanding how the healthy eye gets older, we may be able to work on new ways to use the eyes to determine the risk of people on developing diseases such as Alzheimer’s.”