Exosome engineering: The promise and peril of targeted delivery for treating ocular diseases

In the absence of acceptable cures for ocular diseases, stem cells and their paracrine agents, including exosomes, have become a promising therapeutic approaches. Exosomes are lipid spherical bilayer-encased particles and the smallest subtype of extracellular vehicles (EVs) that are secreted by cells to facilitate intercellular communication in the form of lipids, proteins, mRNAs, and small RNAs. Recent advances in exosome-based therapeutics have witnessed unique opportunities for treating ocular diseases, including autoimmune diseases, traumatic diseases, chorioretinal diseases, and uveal melanoma. Many studies demonstrated that exosomes, in particular, bioengineered exosomes have an impressive effect on target cells. The utilization of exosomes as delivery vectors to encapsulate both therapeutic genes and drugs, surface modification, and encapsulation by biomaterial could yield higher efficacy and avoid unnecessary immune responses. Several studies demonstrated the therapeutic effects of stem cells are due to engineered exosomes. However, exosome-based therapies also show some potential ocular risks. In this review, we first present the origins and general introduction to exosomes. We then provide an overview of the surface modification of MSC-derived exosomes, drug-loaded exosomes, bioengineering, and biomaterial-based exosomes. Eventually, we discussed available applications, their potential risks, and proposed future perspectives to address the translation and underlying issues related to ocular disease.