Currently, extracellular vesicles (EVs)—nano-sized "cellular messengers" enriched with bioactive molecules such as proteins, lipids, and nucleic acids—have garnered attention for their low immunogenicity, engineering flexibility, and excellent biocompatibility.
A recent comprehensive review published in Acta Ophthalmologica, titled "Advances in exosome therapies in ophthalmology: From bench to clinical trial", evaluates the latest progress and challenges in translating exosome-based therapies from bench to bedside.
Unveiling the Role of Exosomes in Multiple Ocular Diseases
The review extensively discusses the therapeutic applications of exosomes in various ocular disease models, ranging from corneal injuries and glaucoma neuroprotection to retinal disorders (e.g., diabetic retinopathy, age-related macular degeneration) and ocular surface inflammation and tissue repair. Studies indicate that exosomes cargo can modulate key pathophysiological processes, including cell proliferation, migration, differentiation, angiogenesis, and inflammatory responses.
Glaucoma remains one of the leading causes of irreversible blindness worldwide. While conventional treatments primarily focus on intraocular pressure (IOP) reduction, they provide limited benefit for restoring already-damaged optic nerves. Research shows that exosomes carrying neuroprotective microRNAs (e.g., miR-486-5p, miR-106a-5p) can promote retinal ganglion cell (RGC) survival, reduce axonal degeneration, and help preserve visual function following intravitreal injection. Periodic administration (weekly or monthly) has shown efficacy, although sustained dosing is required due to the short-term nature of neuroprotection.
Uveitis, an inflammatory disease often triggered by immune dysregulation, can lead to photophobia, blurred vision, and irreversible vision loss. Conventional treatments such as corticosteroids and immunosuppressants are often accompanied by significant long-term side effects. However, studies reveal that mesenchymal stem cell–derived exosomes, which contain immunomodulatory factors like TSG-6, can attenuate retinal structural damage and suppress pro-inflammatory responses in autoimmune models.
Dry eye disease has become a modern-day "civilization illness," affecting millions globally. While artificial tears provide temporary relief, they do not address underlying ocular surface damage. Clinical trials (e.g., NCT04213248) are underway to evaluate umbilical cord–derived stem cell exosomes for improving tear secretion, repairing ocular surface damage, and suppressing CD8⁺ CD28⁻ T-cell activity—offering immune modulation and anti-fibrotic effects.
Retinal ischemia, caused by inadequate blood supply, remains difficult to treat using conventional therapies. Studies suggest that exosomes delivering miR-222 or miR-126 can regulate HMGB1 signaling and NLRP3 inflammasome activity, reducing retinal edema and pathologic neovascularization, thereby promoting tissue repair. Similarly, in diabetic retinopathy, a common complication of diabetes, current interventions such as laser photocoagulation or anti-VEGF injections have limitations in addressing vascular leakage and macular edema.
Age-related macular degeneration (AMD) is a leading cause of visual impairment among the elderly, with few effective treatment options. Research has shown that blood-derived exosomes enriched in miR-626 and miR-485-5p are associated with the pathogenesis of wet AMD. Meanwhile, stem cell–derived exosomes carrying neurotrophic and antioxidant molecules may mitigate oxidative stress and support optic nerve regeneration.
The review further explores exosome delivery routes—such as topical eye drops, intravitreal, and subconjunctival injections—as well as strategies to enhance bioavailability and tissue distribution. It also summarizes ongoing and registered clinical trials assessing safety and preliminary efficacy. Nonetheless, several translational challenges remain, including standardization for large-scale production, purity and potency control, and precise dose optimization.
Conclusion
Exosome therapy holds great promise in ophthalmology, offering innovative disease-modifying strategies for conditions unresponsive to traditional treatments. This breakthrough not only synthesizes current research achievements but also provides critical guidance for future basic and translational studies.
Edited by Sparkling Sciences
Source:Sanghani, A., Andriesei, P., Kafetzis, K. N., Tagalakis, A. D., & Yu-Wai-Man, C. (2022). Advances in exosome therapies in ophthalmology-From bench to clinical trial. Acta ophthalmologica, 100(3), 243–252. https://doi.org/10.1111/aos.14932