Electrochemical Biosensors for Exosome Detection: Current Advances, Challenges, and Prospects for Glaucoma Diagnosis.

Glaucoma is a leading cause of irreversible blindness worldwide, with its asymptomatic progression highlighting the urgent need for early, minimally invasive biomarkers. Exosomes derived from the aqueous humor (AH) have emerged as promising candidates, as they carry proteins, nucleic acids, and lipids that reflect the physiological and pathological state of ocular tissues such as the trabecular meshwork and ciliary body. However, their low abundance, nanoscale size, and the limited volume of AH complicate detection and characterization. Conventional methods, including Western blotting, PCR or mass spectrometry, are labor-intensive, time-consuming, and often incompatible with microliter-scale samples. Electrochemical biosensors offer a highly sensitive, rapid, and low-volume alternative, enabling the detection of exosomal surface markers and internal cargos such as microRNAs, proteins, and lipids. Recent advances in nanomaterial-enhanced electrodes, microfluidic integration, enzyme- and nanozyme-mediated signal amplification, and ratiometric detection strategies have significantly improved sensitivity, selectivity, and multiplexing capabilities. While most studies focus on blood or serum, these platforms hold great potential for AH-derived exosome analysis, supporting early-stage glaucoma diagnosis, monitoring of disease progression, and evaluation of therapeutic responses. Continued development of miniaturized, point-of-care electrochemical biosensors could facilitate clinically viable, noninvasive exosome-based diagnostics for glaucoma.