New findings from a study conducted on tear extracellular vesicles (tEVs) from keratoconus (KC) patients may pave the way for further research into non-invasive treatments for this patient base.
Tell me about extracellular vesicles.
Extracellular vesicles (EVs) are lipid-bound vesicles involved in cell-cell communication by transporting DNA, RNA, and proteins between cells. EVs are found in the cornea and have been reported to assist in corneal epithelium wound healing; however, their exact role in corneal pathobiology is still unknown.
While tEVs have been observed in conditions such as dry eye, Sjögren’s syndrome, and primary open-angle glaucoma, this is the first time they have been identified and had their phenotype assessed in relation to keratoconus.
Talk about the study.
Researchers processed and analyzed tear samples using the ExoView R100 (NanoView Biosciences). The collected tEVs underwent tetraspanin fingerprinting to identify their phenotype, and then statistical analyses were performed. Tears were passively collected from the lateral meniscus of 10 healthy subjects (five male, five female) and nine subjects with keratoconus (four male, five female). The average age for the healthy cohort was 55.5±18.69 years old and 32.2±9.17 for the KC cohort.
What else?
Keratoconus severity was measured using the ABCD grading system. Group 1 was the least severe KC group with an anterior radius curvature (ARC) converted to dioptric values of <48.0 D. This was followed by group 2 with an ARC of <53.0 D, group 3 with an ARC of <55.0 D, and group 4 with an ARC of >55.0 D; however, no subjects in the study met the criteria for inclusion in this group. Within the KC cohort, there were four subjects in groups 1 and 2 and 1 subject in group 3.
What did they find?
The tetraspanin fingerprint results for the tEVs in all study subjects showed a similar phenotype, with the largest cohort of particles being CD9+. A significant decrease in CD63+/CD9+ and CD63+/CD81+/CD9+ particles were found in the tEVs of male keratoconus subjects (p<0.05), which could indicate a reduced immune response ability in keratoconus patients. However, this pattern was not observed in females compared to healthy subjects.
Neither healthy nor keratoconus tEVs showed differences in the total number of tEVs, but significant differences were noted between the sexes (p<0.05), with male keratoconus subjects having a higher count of tEVs.
Significance?
The use of tears in keratoconus studies provides an easily-accessible, minimally-invasive, and cost-effective resource which can be leveraged to better understand the disease. In the future, much larger cohorts are needed in both healthy and keratoconus subjects to accurately determine particle differences in tEVs.
Considering the proximity of tear fluid to the cornea and the number of conditions that could be affected by the presence of tEVs, understanding their potential role and function in corneal health and disease states is of significant interest to researchers and clinicians alike.