Extracellular vesicles (EVs) are small membrane-bound particles that play a vital role in intercellular communication by facilitating the transfer of molecular cargo. In this review, we provide an overview of EV biology in corneal diseases, along with current approaches to therapeutic uses of EVs. Since EVs generally retain surface markers indicative of their cell of origin, they possess a degree of tissue specificity, which benefits drug delivery systems and highlights their potential as biomarkers to study disease processes. Further advances in technology and methodology will accelerate our understanding of EVs and help guide the field towards improved diagnostic techniques and therapeutic targets. We summarize EVs and their potential impact in medicine with a discussion of the limitations that remain in current approaches, as well as areas to focus on for future growth.

Keratoconus (KC) is a degenerative corneal disease, characterized by stromal thinning and abnormal ECM remodeling, leading to fibrosis. Corneal fibrosis is a leading cause of visual impairment. Corneal stromal keratocytes differentiate into myofibroblasts, which alters extracellular matrix (ECM) protein deposition. Nintedanib (NIN) is an antifibrotic FDA-approved tyrosine kinase inhibitor, but its function in the cornea is largely unknown. This study examined the impact of NIN within the human corneal stromal microenvironment. Healthy corneal stromal fibroblasts (HCFs) and KC fibroblasts (HKCs) in 2D and 3D in vitro cultures were treated with 1 μM or 2.5 μM NIN. Cell types were evaluated in 2D cultures for metabolic activity, viability, and migration. Protein expression of alpha-smooth muscle actin (α-SMA), collagens (COLs) 1, 3, and 5, cellular fibronectin containing extra domain A (EDA-FN), and thrombospondin-1 (TSP-1) were evaluated in 3D cultures. NIN reduced metabolic activity in HKCs without affecting cell viability. NIN reduced cell migration, downregulated COL3, COL5, EDA-FN, and TSP-1 expression in HCFs and HKCs. COL1 was upregulated in HCFs, whereas α-SMA was upregulated in HKCs. Overall, these findings demonstrate that NIN modulates corneal stromal cell migration and fibrotic marker expression, highlighting its potential as a therapeutic strategy for reducing corneal fibrosis associated with keratoconus.