Exosomes are a group of vesicles that package and transport DNA, RNA, proteins, and lipids to recipient cells. They can be derived from blood, saliva, urine, and/or other biological tissues. Their impact on several diseases, such as neurodegenerative, autoimmune, and ocular diseases, have been reported, but not fully unraveled. The exosomes that are derived from saliva are less studied, but offer significant advantages over exosomes from other sources, due to their accessibility and ease of collection. Thus, their role in the pathophysiology of diseases is largely unknown. In the context of ocular diseases, salivary exosomes have been under-utilized, thus creating an enormous gap in the literature. The current review discusses the state of exosomes research on systemic and ocular diseases and highlights the role and potential of salivary exosomes as future ocular therapeutic vehicles.

Corneal transplantation remains a critical treatment option for individuals with corneal disorders, but it faces challenges such as rejection, high associated medical costs, and donor scarcity. A promising alternative for corneal replacement involves fabricating artificial cornea from a patient’s own cells. Our study aimed to leverage bioprinting to develop a corneal model using human corneal stromal cells embedded in a collagen-based bioink. We generated both cellular and acellular collagen I (COL I) constructs. Cellular constructs were cultured for up to 4 weeks, and gene expression analysis was performed to assess extracellular matrix (ECM) remodeling and fibrotic markers. Our results demonstrated a significant decrease in the expression of COL I, collagen III (COL III), vimentin (VIM), and vinculin (VCL), indicating a dynamic remodeling process towards a more physiologically relevant corneal ECM. Overall, our study provides a foundational framework for developing customizable, corneal replacements using bioprinting technology. Further research is necessary to optimize the bioink composition and evaluate the functional and biomechanical properties of these bioengineered corneas.

Extracellular vesicles (EVs) are structures that are produced from cells and participate in intercellular communication by transporting biomolecules from one cell to another. EVs have been shown to travel short and far distances in the body and are tissue-specific. EVs are not only found in tissues, but they can also be found in practically all bodily fluids, such as tears, saliva, cerebral spinal fluid, blood, etc. Even though EVs can be collected non-invasively from tears and saliva, only small volumes can be collected at a time, which can cause issues in obtaining enough EVs to analyze proteins. The scanner discussed in this paper is a nanoparticle analyzer that provides a solution to this problem, allowing us to characterize and study the phenotype, size, and total particle count of EVs from as little as 1 µL of biological fluid. This protocol will expand the knowledge of EVs from small volumes of samples that are difficult to extract from patients. This could enhance patient comfort and potentially identify new therapeutic targets for a range of diseases and disorders.

This study investigated the interplay between transforming growth factor beta (TGF-β1/T1 and TGF-β3/T3), and sex hormone receptors using our 3D in vitro cornea stroma model. Primary human corneal fibroblasts (HCFs) from healthy donors were plated in transwells at 10⁶ cells/well and cultured for four weeks. HCFs were supplemented with stable vitamin C (VitC) and stimulated with T1 or T3. 3D construct proteins were analyzed for the androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα) and beta (ERβ), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), gonadotropin-releasing hormone receptor (GnRHR), KiSS1-derived peptide receptor (KiSS1R/GPR54), and follicle-stimulating hormone subunit beta (FSH-B). In female constructs, T1 significantly upregulated AR, PR, ERα, FSHR, GnRHR, and KiSS1R. In male constructs, T1 significantly downregulated FSHR and FSH-B and significantly upregulated ERα, ERβ, and GnRHR. T3 caused significant upregulation in expressions PR, ERα, ERβ, LHR, FSHR, and GNRHR in female constructs, and significant downregulation of AR, ERα, and FSHR in male constructs. Semi-quantitative Western blot findings present the interplay between sex hormone receptors and TGF-β isoforms in the corneal stroma, which is influenced by sex as a biological variable (SABV). Additional studies are warranted to fully delineate their interactions and signaling mechanisms.

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.

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.