Human tears could carry a flood of useful information.
With just a few drops, a new technique can spot eye disease and even glimpse signs of diabetes, scientists report July 20 in ACS Nano. Nanoscale small extracellular vesicles (sEVs, exosomes) in tears allow us to investigate the multisignatures of diseases. However, the translations of tear sEVs for biomarker discovery and clinical diagnostics are practically limited by low recovery, long processing time, and small sample volume. Here, we report an incorporated tear-exosomes analysis via rapid-isolation system (iTEARS) via nanotechnology to discover the secrets of ocular disorders and systemic diseases. We isolate exosomes rapidly with high yield and purity from a few teardrops (∼10 μL) within 5 min via nanoporous membrane-based resonators for the quantitative detection and biomarker discovery through proteomic and transcriptomic analysis. We have identified 904 proteins, among which 228 proteins are discovered, 426 proteins are detected from exosomes of dry eye disease, and demonstrate CALML5, KRT6A, and S100P for the classification of dry eye disease. We have also investigated 484 miRNAs in tear exosomes and show miR-145-5p, miR-214-3p, miR-218-5p, and miR-9-5p are dysregulated during diabetic retinopathy development. We believe iTEARS can be used for improving molecular diagnostics via tears to identify ocular disorders, systemic diseases, and numerous other neurodegenerative diseases and cancer. Current clinical studies pose significant challenges in distinguishing disease subtypes with accurate molecular signatures and tracking the disease progression in a non-invasive way.Since small extracellular vesicles (sEVs, exosomes) reveal specific functions in various biological processes, including immune regulation, angiogenesis, tumor invasion, and cell migration, exosome-based liquid biopsy technology has offered an attractive alternative to disease classification and prognostic prediction.
“We wanted to demonstrate the potential of using tears to detect disease,” says Fei Liu, a biomedical engineer at Wenzhou Medical University in China. It’s possible the droplets could open a window for scientists to peer into the entire body, he says, and one day even let people quickly test their tears at home.
Like saliva and urine, tears contain tiny sacs stuffed with cellular messages (SN: 9/3/13). If scientists could intercept these microscopic mailbags, they could offer new intel on what’s happening inside the body. But collecting enough of these sacs, called exosomes, is tricky. Unlike fluid from other body parts, just a trickle of liquid leaks from the eyes.
So Liu’s team devised a new way to capture the sacs from tiny volumes of tears. First, the researchers collected tears from study participants. Then, the team added a solution containing the tears to a device with two nanoporous membranes, vibrated the membranes and sucked the solution through. Within minutes, the technique lets small molecules escape, leaving the sacs behind for analysis.
The results gave scientists an eyeful. Different types of dry-eye disease shed their own molecular fingerprints in people’s tears, the team found. What’s more, tears could potentially help doctors monitor how a patient’s diabetes is progressing.
Now, the scientists want to tap tears for evidence of other diseases as well as depression or emotional stress, says study coauthor Luke Lee, a bioengineer at Harvard Medical School. “This is just the beginning,” he says. “Tears express something that we haven’t really explored.”
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