title: Revisited microanatomy of the corneal endothelial periphery: new evidence for continuous centripetal migration of endothelial cells in humans.
abstract: The control of corneal transparency depends on the integrity of its endothelial monolayer, which is considered nonregenerative in adult humans. In pathological situations, endothelial cell (EC) loss, not offset by mitosis, can lead to irreversible corneal edema and blindness. However, the hypothesis of a slow, clinically insufficient regeneration starting from the corneal periphery remains debatable. The authors have re-evaluated the microanatomy of the endothelium in order to identify structures likely to support this homeostasis model. Whole endothelia of 88 human corneas (not stored, and stored in organ culture) with mean donor age of 80 ± 12 years were analyzed using an original flat-mounting technique. In 61% of corneas, cells located at the extreme periphery (last 200 μm of the endothelium) were organized in small clusters with two to three cell layers around Hassall-Henle bodies. In 68% of corneas, peripheral ECs formed centripetal rows 830 ± 295 μm long, with Descemet membrane furrows visible by scanning electron microscopy. EC density was significantly higher in zones with cell rows. When immunostained, ECs in the extreme periphery exhibited lesser differentiation (ZO-1, Actin, Na/K ATPase, CoxIV) than ECs in the center of the cornea but preferentially expressed stem cell markers (Nestin, Telomerase, and occasionally breast cancer resistance protein) and, in rare cases, the proliferation marker Ki67. Stored corneas had fewer cell clusters but more Ki67-positive ECs. We identified a novel anatomic organization in the periphery of the human corneal endothelium, suggesting a continuous slow centripetal migration, throughout life, of ECs from specific niches.
authors.affiliation: Corneal Graft Biology, Engineering and Imaging Laboratory, Federative Institute of Research in Sciences and Health Engineering, Faculty of Medicine, Jean Monnet University, Saint-Etienne, France.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: He
authors.forename: Nelly
authors.initials: N
authors.lastname: Campolmi
authors.forename: Philippe
authors.initials: P
authors.lastname: Gain
authors.forename: Binh Minh
authors.initials: BM
authors.lastname: Ha Thi
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Dumollard
authors.forename: Sébastien
authors.initials: S
authors.lastname: Duband
authors.forename: Michel
authors.initials: M
authors.lastname: Peoc'h
authors.forename: Simone
authors.initials: S
authors.lastname: Piselli
authors.forename: Olivier
authors.initials: O
authors.lastname: Garraud
authors.forename: Gilles
authors.initials: G
authors.lastname: Thuret
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D048430:Cell Shape; D002470:Cell Survival; D003886:Descemet Membrane / Q000166:cytology*; D042783:Endothelial Cells / Q000502:physiology*; D004728:Endothelium, Corneal / Q000166:cytology*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D055153:Stem Cell Niche; D046509:Tissue Culture Techniques; D055815:Young Adult
chemical_list: D000943:Antigens, Differentiation; D019394:Ki-67 Antigen