Bovine Posterior Limbus: An Evaluation of an Alternative Source for Corneal Endothelial and Trabecular Meshwork Stem/Progenitor Cells

Abstract

A growing body of evidence has revealed that stem-like cells in the posterior limbus of the eye between the corneal endothelium (CE) and trabecular meshwork (TM) may be able to rejuvenate these tissues in disease. However, these cells have not been clearly defined and we have named them PET cells (progenitor cells of the endothelium and trabeculum). A good and inexpensive animal model for PET cells is lacking, so we investigated bovine eyes as an effective large tissue source. We showed the presence of stem/progenitor cells in the bovine CE, transition zone, and TM in situ. Floating spheres cultured from the CE and TM showed similar stem cell marker expression patterns. Both the CE and TM spheres were bipotent and highly proliferative, but with limited secondary sphere-forming capability. They were highly prone to differentiate back into the cell type of their tissue of origin. It is speculated that the PET cells become more tissue-specific as they migrate away from their niche. Here, we showed that PET cells are present in the posterior limbus of bovine eyes and that they can be successfully cultured and expanded. PET cells represent an attractive target for developing new treatments to regenerate both the CE and TM, thereby reducing the requirement for donor tissue for corneal transplant and invasive treatments for glaucomatous patients.

Translational issues for human corneal endothelial tissue engineering

“…Besides the effects of interspecies age discrepancies that have been described earlier, it has also been suggested that mechanisms such as the arrest of animal CECs at a more favourable step within the G 1 phase is responsible for their heightened cellular proliferative responses in contrast to human CECs (Joyce et al , ; Van Horn et al , ). A recent study also identified the expression of stem cell markers, such as telomerase and nestin, throughout the entire bovine corneal endothelial monolayer (Yu et al , ), which may explain the increased capacity of bovine CECs for cell division.…”

Biomaterials for Regenerative Medicine Approaches for the Anterior Segment of the Eye

“…[5] Evidence suggests that these progenitor cells can differentiate into either corneal endothelial cells or trabecular meshwork cells. [5,10,11] Whikehart et al demonstrated that the cells located at the peripheral corneal endothelium displayed increased cell density as well as increased telomerase activity, combined with Bromodeoxyuridine labeling within the insert region and also within the trabecular meshwork. [12] Following argon laser trabeculoplasty of ex vivo organ cultures there was an increase in cell division within cells in the nonfiltering insert region of the trabecular meshwork [13] and the cells migrated into the posterior trabecular meshwork.…”

“…Currently, the most up to date surgical treatment for glaucoma related to this cause is to create a drainage channel through the blocked tissue; however, there is evidence that there are trabecular meshwork progenitor cells at the inner surface of the limbus and that these might be able to be used to repopulate the trabecular meshwork. [11] So, the question arises whether it would be useful to have a scaffold on which to grow these cells to reintroduce them to the trabecular meshwork?…”

Quantification of the Posterior Cornea Using Swept Source Optical Coherence Tomography

“…1 ). The posterior corneal surface, from center to periphery, consists of the following regions: (1) central endothelium; (2) peripheral endothelium, including a 0.2-mm wide region termed the extreme peripheral endothelium; 23 (3) Schwalbe's line (SL), defined as the terminal edge of the endothelium and DM; (4) transition zone, also known as the smooth zone or Zone S, previously defined as a smooth region without endothelium or trabecular meshwork (TM) fibers; 22 , 24 , 25 (5) TM; and (6) the scleral spur (SS), a scleral protrusion in the anterior chamber. Of note, the TZ sometimes is referenced in the literature as Schwalbe's line; we define Schwalbe's line only as the DM edge, while the adjacent 40 to 200 μm region is the TZ.…”