Stem cell markers in the human posterior limbus and cornealendothelium of unwounded and wounded corneas

[摘要] Purpose: The corneal endothelium is a monolayer of cells in theposterior cornea that is responsible for maintaining a clear cornea.Corneal endothelial cells may be induced to divide, but it has been heldthat they do not divide in the normal cornea of an adult human. Somestudies have suggested that a stem cell population for the cornealendothelium exists. This population could give rise to mature cornealendothelial cells and may reside either in the peripheral cornealendothelium or in the adjacent posterior limbus. This study wasinitiated to demonstrate the presence of such stem cells in the regionof the posterior limbus and to show the response of these cells tocorneal wounding.Methods: Unwounded and wounded corneas with their attached limbalsections were analyzed by immunofluorescence for the presence of nestin,telomerase, Oct-3/4, Pax-6, Wnt-1, and Sox-2. Alkaline phosphataseactivity was observed with an enzyme-based reaction that produced afluorescent product.Results: In the unwounded cornea, stem cell markers nestin, alkalinephosphatase, and telomerase were found in the trabecular meshwork (TM)and in the transition zone between the TM and the corneal endothelialperiphery (including Schwalbe's line). Telomerase was also present inthe peripheral corneal endothelium. When wounded corneas and theirattached limbii were tested, the same markers were found. However, afterwounding, additional stem cell markers, Oct-3/4 (in the TM) and Wnt-1(in both the TM and the transition zone), appeared. Moreover, thedifferentiation markers Pax-6 and Sox-2 were seen. Pax-6 and Sox-2 werealso manifest in the peripheral endothelium post-wounding.Conclusions: Well-documented specific stem cell markers were foundin the TM and the transition zone of the human posterior limbus.Wounding of the corneas activated the production of two additional stemcell markers (Oct-3/4, Wnt-1) as well as two differentiation markers(Pax-6, Sox-2), the latter of which also appeared in the cornealendothelial periphery. It is suggested that stem cells reside in theposterior limbus and respond to corneal wounding to initiate anendothelial repair process. The stem cells may also contribute to anormal, slow replacement of corneal endothelial cells.

[学科分类] 生物化学/生物物理