Researchers have uncovered new techniques that can manipulate the functioning of the trabecular meshwork and, potentially, regulate intraocular pressure (IOP). This knowledge may influence the development of future glaucoma treatment.

Collagen secretion to the extracellular matrix, and its formation by trabecular meshwork (TM) cells, is “at least partially regulated by nonpigmented ciliary epithelium [NPCE] extracellular vesicles [EVs],” says the study published in the Journal of Cellular and Molecular Medicine.

“These are important observations that should influence future glaucoma research, focusing on facilitating aqueous humor outflow and lowering IOP,” investigators report. 


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The study was conducted following extraction of NPCE derived EVs with a precipitation method. Size and concentration were established with tunable resistive pulse sensing technology. Investigators evaluated if adding NPCE EVs to TM cells impacted formation and structure of collagen fibers secreted via TM cells by adding those cells to TM cells every 24 hours for 3 days. A control of untreated TM cells was also used. 

Investigators employed Sirius Red reagent to mark total collagen of untreated or treated TM cells. Samples were then washed with PBS 3 times and placed on slides. A FV1000-IX81 confocal microscope equipped with an 60× objective analyzed images. Collagen type I expression levels in the extracellular matrix of TM cells were quantified with cell Western analysis. 

“We found that nonpigmented ciliary epithelium extracellular vesicles were very effective at preventing collagen fibers formation by the trabecular meshwork cells, and their secretion to the extracellular matrix was significantly reduced (P < .001),” investigators report. 

They also observed morphological changes in the extracellular matrix of TM cells. 

“Our study indicates that nonpigmented ciliary epithelium extracellular vesicles can be used to control collagen type I fibrillogenesis in trabecular meshwork cells. These fibrils net-like structure is responsible for remodeling the extracellular matrix. Moreover, we suggest that targeting collagen type I fibril assembly may be a viable treatment for primary open-angle glaucoma abnormal matrix deposition of the extracellular matrix,” explain investigators.

“Further studies of other types of collagens present in the TM are necessary to elucidate the role of lack of synthesis of ECM components in the outflow pathway and their effect on the IOP elevation mechanism.”

Reference

Tabak S, Schreiber‐Avissar S, Beit‐Yannai E. Trabecular meshwork’s collagen network formation is inhibited by non‐pigmented ciliary epithelium‐derived extracellular vesicles. J Cell Mol Med. Published online March 1, 2021. doi:10.1111/jcmm.16408