Corneal Stromal Stem Cell-Derived Extracellular Vesicles Attenuate ANGPTL7 Expression in the Human Trabecular Meshwork.
Publication Year:
2025
PubMed ID:
39847376
Funding Grants:
Public Summary:
The trabecular meshwork (TM) is a spongy, mesh-like tissue inside the eye that acts like a drain, regulating the flow of fluid and maintaining healthy eye pressure. In this study, extracellular vesicles (EVs) released from the stem cells of the corneal stroma were used in combination with the corticosteroid dexamethasone (Dex) to determine the effect of these EVs on fibrosis. The expression of ANGPTL7, a gene associated with fibrosis and IOP elevation, was reduced with EV treatment. Therefore, EVs can potentially be used to reduce IOP elevation in the TM.
Scientific Abstract:
PURPOSE: Regulating intraocular pressure (IOP), mainly via the trabecular meshwork (TM), is critical in developing glaucoma. Whereas current treatments aim to lower IOP, directly targeting the dysfunctional TM tissue for therapeutic intervention has proven challenging. In our study, we utilized Dexamethasone (Dex)-treated TM cells as a model to investigate how extracellular vesicles (EVs) from immortalized corneal stromal stem cells (imCSSCs) could influence ANGPTL7 and MYOC genes expression within TM cells. METHODS: Human TM cell lines were isolated and cultured from donor corneoscleral rims. EVs were purified from imCSSC conditioned media (CM) using size exclusion chromatography and characterized by nanoparticle tracking analysis, transmission electron microscopy (TEM), and ExoView technology. TM cells were treated with either Dex alone or with EVs for 5 days. Quantitative polymerase chain reaction (PCR) was carried out to quantify the mRNA level of MYOC and ANGPTL7. RESULTS: A notable increase in the expression levels of MYOC and ANGPTL7 genes was observed compared with untreated TM cells (control). Furthermore, upon comparing Dex-treated TM cells with those receiving both Dex and EV treatments, a statistically significant reduction in ANGPTL7 expression (P < 0.05) was detected. CONCLUSIONS: The present study demonstrates that imCSSCs-derived EVs can effectively decrease the expression of ANGPLT7, a gene associated with fibrosis and implicated in the abnormal elevation of IOP in patients with glaucoma. TRANSLATIONAL RELEVANCE: Our study shows that imCSSC-derived EVs can specifically target ANGPTL7 expression, making them a promising preclinical therapy for glaucoma.
