“What’s amazing about the eye is we can look inside and see diseases happening,” but in real-time?
A group of scientists successfully mapped nearly 6,000 proteins across various eye cells using small samples of eye fluid typically extracted during surgical procedures.
Announced in the ‘Cell’ journal on October 19, the team harnessed artificial intelligence to develop a “protein age gauge” using this data. This tool can estimate an individual’s age by analyzing their protein composition.
Findings indicated that conditions like diabetic retinopathy and uveitis lead to rapid aging in certain cells. Intriguingly, the study also found proteins linked to Parkinson’s disease present in the eye fluid, hinting at potential avenues for its earlier detection.
“What’s amazing about the eye is we can look inside and see diseases happening in real time,” remarked senior researcher Vinit Mahajan, an esteemed ophthalmologist and faculty at Stanford University. “Our primary focus was to connect those anatomical changes to what’s happening at the molecular level inside the eyes of our patients.”
Sampling the eye presents unique challenges. Unlike other organs, the eye can’t regenerate, making tissue biopsies harmful. The solution? Liquid biopsies, which provide glimpses into the proteins present, albeit with certain limitations.
To overcome these, Mahajan’s group employed a sophisticated technique to profile proteins from 120 liquid samples sourced from patients’ eye fluids, identifying a staggering 5,953 proteins—a monumental jump from past studies. The team’s innovative software, TEMPO, could then map these proteins to their originating cells.
When probing the link between diseases and molecular aging, the scientists developed an AI-driven model that evaluates the eye’s molecular age through 26 key proteins. The findings were startling: while healthy eyes mirrored actual age, disease-stricken eyes reflected advanced molecular aging. Especially in severe diabetic retinopathy cases, the molecular age could outpace the actual age by three decades. Some of these molecular age shifts were visible even before traditional symptoms emerged.
Adding another layer of complexity, proteins typically linked posthumously to Parkinson’s disease were spotted. Current diagnostic tools fall short in detecting these, making Parkinson’s notoriously hard to diagnose early on. Yet, by examining eye fluid, earlier diagnoses, and subsequent treatment monitoring may soon be possible.
The study’s implications stretch far and wide. It suggests aging could be specific to organs or even cells, a revelation with profound impacts on precision medicine and future research.
“These findings demonstrate that our organs are aging at different rates,” pointed out first author and ophthalmologist Julian Wolf of Stanford University. “The use of targeted anti-aging drugs could be the next step in preventative, precision medicine.”
“If we’re going to use molecular therapies, we should be characterizing the molecules in our patients,” Mahajan added. “I think reclassifying patients based on their molecular patterns and which cells are being affected can really improve clinical trials, drug selection, and drug outcomes.”
Looking ahead, they are eager to expand their sample size and disease spectrum. Additionally, they believe their technique holds promise for other challenging-to-sample organs, suggesting that fluids from the brain, joints, or kidneys could be next in line for such molecular scrutiny.
Source: 10.1016/j.cell.2023.09.012
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