Researchers have identified cell-specific proteins in eye fluid and used AI to determine which proteins accelerated aging in particular diseases.
Understanding the cellular origin of these disease-driving proteins may lead to precision treatments and more informed clinical trials. Analysing cells is an essential part of understanding disease mechanisms.
Stanford Medicine researchers did just that, developing a technique of examining cell-specific proteins found in aqueous humor, the nourishing fluid inside the front part of the eye, and using AI to determine a person’s ‘eye age’ and how it’s affected by disease.
Using a technique they developed called TEMPO, they traced proteins to a cell type where the RNA that creates that protein resides.
Aqueous humor was also collected from people with three types of eye diseases: diabetic retinopathy, which causes blood vessels in the eye to leak, leading to vision loss; retinitis pigmentosa, which causes light-sensitive cells in the back of the eye to break down; and, uveitis, inflammation inside the eye.
Comparing diseased eye fluid with healthy fluid, the researchers found that proteins in diseased eyes indicated a higher cellular age. In patients with early-stage diabetic retinopathy, the cells were 12 years older, and in those with late-stage retinopathy, 31 years older. In patients with retinitis pigmentosa and uveitis, the cells were 29 years older.
The AI model also found that the cells responsible for indicating increased ocular age differed across the diseases studied. In late-stage diabetic retinopathy, it was vascular cells, retinal cells in retinitis pigmentosa, and immune cells in uveitis.
The researchers found that some of these disease-affected cells are not commonly targeted by treatment, suggesting there needs to be a re-evaluation of current therapies.
Importantly, the researchers found that some cells showed accelerated aging before symptoms appeared, meaning that treatment could be started earlier to avoid irreparable damage.
Targeting both aging and disease cells could make treatment more effective because the two act separately but simultaneously to cause eye damage, the researchers say.
“It’s as if we’re holding these living cells in our hands and examining them with a magnifying glass,” said Mahajan.