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Cheng Li, Wei Li, ZUGUO LIU, JIng Li; APR-246/PRIMA-1Met inhibits and reverses squamous metaplasia in human conjunctival epithelium. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3853. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Squamous metaplasia is a common pathological condition in ocular surface diseasesfor which there is no therapeutic medication in clinic. In this study, we investigated the effect of a small molecule APR-246/PRIMA-1Met on squamous metaplasia in human conjunctival epithelium.
Human conjunctival explants were cultured for up to 12 days under airlift conditions. Epithelial cell differentiation and proliferation were assessed based on K10, K14, K19, Pax6, MUC5AC, and p63 immunostaining patterns. β-catenin and TCF-4 immunofluorescent staining and real-time PCR characterized Wnt signaling pathway involvement. Pterygium clinical samples were cultured under airlift conditions with or without APR-246 for 4 days. p63, K10, β-catenin and TCF-4 expression in pterygial epithelium was determined by immunofluorescent staining and real-time PCR.
Airlifting conjunctival explants resulted in increased stratification and intrastromal epithelial invagination. Such pathology was accompanied by increases in K10, K14 and p63 expression whereas K19 and Pax6 levels declined compared to those in freshly isolated tissue. On the other hand, APR-246 reversed all of these declines in K10, K14, and p63 expression. Furthermore, K19 and Pax6 increased along with rises in goblet cell density. These effects of APR-246 were accompanied by near restoration of normal conjunctival epithelial histology. APR-246 also reversed squamous metaplasia in pterygial epithelium that had developed after 4 days ex vivo culture.
Reductions in squamous metaplasia induced by APR-246 suggest it may provide a novel therapeutic approach in different squamous metaplasia associated ocular surface diseases.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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