Extracellular vesicles (EVs) are increasingly recognized as programmable bioactive carriers in non-viral gene delivery and adaptable bioengineering platforms. Beyond their roles as natural nanocarriers in intercellular communication, EVs can promote ocular surface repair and retinal neuroprotection with potential for low immunogenicity and high biocompatibility. Bioengineering now enables cargo encapsulation, surface targeting, and integration of EVs with biomaterial platforms to enhance tissue penetration, retention, and precision delivery. The emergence of induced pluripotent stem cell-derived EVs (iMSC-EVs) offers improved batch uniformity and potential for personalized therapy. However, progress hinges on resolving knowledge gaps in ocular EV biology, standardizing isolation and storage, scaling reproducible manufacturing, and executing focused clinical trials. We synthesize the current developments and outline how EVs are moving from biological mediators to engineered therapeutics to accelerate the translation of EV diagnostics and therapeutics for eye diseases.

Diabetic neuropathy (DN) is the most common complication of diabetes mellitus (DM) and often involves the cornea, where progressive loss of nerve fibers contributes to impaired corneal sensitivity and wound healing defects. Current treatments are limited, underscoring the need for a regenerative therapy. Here we show that a non-invasive neural modulation therapy, transcutaneous electrical stimulation (ES), significantly restore the nerve density and sensory function in both streptozotocin-induced DM mice and in vitro isolated trigeminal ganglia (TG) neurons. Transcriptomics analysis of TGs from in vivo ES points to ion transport and Ca²⁺ signaling alteration. Consistently, membrane potential recording in TGs shows a rapid hyperpolarization upon ES accompanied by increased [Ca²⁺]_i level. Inhibition of potassium intermediate/small conductance calcium-activated channel (KCNN) abolishes the hyperpolarization and neural regeneration effect, whereas activation of KCNN channel significantly enhances nerve regeneration in the STZ model compared with sham treatment. Overall, ES restores corneal nerve density and function via KCNN activation in a diabetic mouse model, offering a novel, non-invasive, and clinically translatable therapeutic strategy for diabetic neuropathy.