Exosomal microRNAs as potential biomarkers and therapeutic targets in corneal diseases

Abstract

Exosomes are a subtype of extracellular vesicle (EV) that are released and found in almost all body fluids. Exosomes consist of and carry a variety of bioactive molecules, including genetic information in the form of microRNAs (miRNAs). miRNA, a type of small non-coding RNA, plays a key role in regulating genes by suppressing their translation. miRNAs are often disrupted in the pathophysiology of different conditions, including eye disease. The stability and easy detectability of exosomal miRNAs in body fluids make them promising biomarkers for the diagnosis of different diseases. Additionally, due to the natural delivery capabilities of exosomes, they can be modified to transport therapeutic miRNAs to specific recipient cells. Most exosome research has primarily focused on cancer, so there is limited research highlighting the importance of exosomes in ocular biology, particularly in cornea-associated pathologies. This review provides an overview of the existing evidence regarding the primary functions of exosomal miRNAs and their potential role in diagnostic and therapeutic applications in the human cornea.

Figure 1

Applications of eye fluid-derived exosomal miRNA as diagnostic biomarkers of corneal diseases. Exosomes from eye fluids can be analyzed for omics data. These exosomes may be useful for diagnosing corneal diseases after marker validation.

Figure 2

Schematic showing the therapeutic potential of exosomes derived from eye fluids or from mesenchymal stem cells (MSCs), induced pluripotent stem cells (iPSCs), limbal epithelial cells (LECs), and limbal stroma cells (LSCs) in corneal repair and regeneration. Isolated vesicles containing small RNAs, proteins, and lipids play a functional role in cellular communication. They can be modified by loading specific miRNA inhibitors or mimics and siRNAs and are delivered either through local injection or systemic delivery. These engineered vesicles have the capability to alter the expression of target genes in damaged cornea cells by attaching complementary oligonucleotides. They also have an impact on the generation of matrix components, the formation of fibroblasts, the transformation of keratocytes, the promotion of corneal epithelial proliferation, the acceleration of wound healing, and the modulation of the immune response. Ultimately, these properties contribute to the regeneration of corneal injuries, homeostasis, and the maintenance of transparency.