Researchers in the US and China have developed a new technique for quickly and accurately diagnosing eye-related diseases, by detecting biomolecular signatures in patients’ tears. Developed by a team led by Luke Lee at Harvard Medical School and Fei Liu at Wenzhou Medical University, the iTEARS system uses oscillating nanoporous membranes to isolate encased biomolecules from impurities, making them far easier to study and classify.
A major challenge faced by current clinical studies is the need to diagnose diseases in non-invasive ways. Valuable information about a wide range of biological processes can be found in exosomes: structures released from nearly all types of living cell, in which complex biomolecules, including proteins, lipids and nucleic acids, are encased in a cell membrane shell. By studying these exosomes, clinicians can identify the biological processes associated with specific diseases, without the need for more intrusive methods.
A particularly useful source of exosomes is patients’ tears – which share key biomolecular components with their blood, and are also far more readily accessible than other fluids in the eye. However, existing techniques for diagnosing patients in this way have so far been limited by long processing times, small sample volumes and low rates of exosome recovery.
In their study, reported in ACS Nano, the researchers introduce a new approach to teardrop analysis, named the “incorporated tear-exosomes analysis via rapid isolation system” (iTEARS). Their method first involves collecting tears on a non-invasive test strip, which is immersed in a salt solution. The fluid then passes between a pair of closely-spaced nanoporous membranes, made from anodic aluminium oxide.
Both membranes are driven to oscillate by the varying pressure difference between the fluid inside them, and the space outside. During these oscillations, small biomolecule fragments could pass through the barriers, while leaving the exosomes trapped inside. Subsequently, the team could remove the exosomes’ cargo from their cell membrane casings, ready for analysis.
Using iTEARS, the researchers analysed the tears of human participants – some healthy, and some suffering from one of a variety of eye-related diseases. For each patient, the technique allowed them to isolate high yields of pure exosomes from just a few teardrops (roughly 10 µl) within just 5 min. Altogether, they identified over 900 types of protein in the samples.
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Out of these, 426 were found in exosomes associated with dry eye disease: a common condition where tears provide insufficient lubrication for the eye. By identifying three specific proteins in a patients’ tears, the researchers could also distinguish between two subtypes of dry eye disease, which each require different treatments.
Further, the researchers found that an excess of four types of RNA molecule was indicative of diabetic retinopathy, a complication of diabetes that damages the retina. Based on this early success, they hope that iTEARS could provide fast, accurate and non-invasive diagnosis for a wide range of eye-related conditions and other diseases.
