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Jiagang Zhao, Joanne Ho, Christine Sutu, Natalie A Afshari; Regulation of YAP activity in human corneal endothelial cells. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4911.
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© ARVO (1962-2015); The Authors (2016-present)
To elucidate a potential mechanism for tightly controlling human corneal endothelium growth, we investigated the function of Yes-associated protein (YAP), a transcriptional effector of Hippo signaling pathway that is important in regulating mammalian organ size. We hypothesize that through interacting with cell scaffold proteins, YAP may play an important role in corneal endothelium maintenance and corneal endothelial cell proliferative capacity.
Human donor corneas were provided by the San Diego Eye Bank. Explant culture was performed on unused donor cornea surgical specimens. Both uncultured and 5-day explant cultured samples were fixed and subjected to flat mount immunohistochemistry analysis. Dissociated primary human corneal endothelial cells were cultured in a defined medium. The expression patterns of YAP, alpha-catenin, and other molecules associated with endothelial mesenchymal transition were analyzed by immunofluorescence staining.
Immunofluorescence staining of YAP in human corneal endothelium specimens showed a pattern of strong cellular membrane association in central cornea, with a shift towards increased cytoplasmic and nuclear localization in peripheral regions. Peripheral corneal endothelial cells also showed increased expression of YAP and Ki67, a proliferative marker. Interestingly, alpha-catenin, a major adherent junction protein that can inhibit YAP by recruitment to the membrane, showed a correlated expression pattern. Increased endothelial mesenchymal transition as well as cell proliferation and mobility of corneal endothelial cells were accompanied by elevated YAP expression and nuclear localization in corneal explant culture.
These findings suggest that YAP activity and its interactions with cell scaffold proteins control homeostasis of corneal endothelium. Manipulation of the Hippo-YAP signaling pathway could be a potential therapeutic approach to treat corneal endothelial diseases.
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