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Ahdeah Pajoohesh-Ganji, Sonali Pal-Ghosh, Gauri Tadvalkar, Mary Ann Stepp; Corneal Goblet Cell Hyperplasia (CGH) Occurs After Wounding The Mouse Ocular Surface. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3507.
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© ARVO (1962-2015); The Authors (2016-present)
To identify the origin of K8+ goblet cell clusters (GCCs) on the mouse ocular surface after 2.5 mm debridement wounds.
BALB/c mice ocular surface was demarcated using a 2.5mm trephine and epithelium was removed using a dulled blade. Mice were sacrificed at 1, 7, 14, and 28 days after wounding. In addition, 1 day old pups were injected with BrdU for 4 days and allowed to mature to 8 wks to visualize slow cycling stem cells. After sacrifice, eyes were enucleated, fixed in methanol and DMSO (4:1), and stored in 100% methanol for Immunofluorescence staining.
K8+ GCCs are located at the corneal periphery adjacent to the limbus in unwounded mouse corneas and. They contain several (3-6) corneal epithelial cells in at least three differentiation states: 1) differentiated cells that are K8+ K12+ Muc5AC+ ki67-, 2) proliferating cells that are K8+ K12+ Muc5AC- ki67+, and 3) label retaining BrdU+ cells that are K8+. As early as one day after injury, GCCs elongate and move towards the wound edge. By 7 days, GCCs disaggregate generating small clusters and individual K8+ cells. At 14 days, the number of GCCs increases over the entire corneal surface. By 28 days, GCCs begin to decrease in number compared to 14 days. The adult mice that were injected with BrdU as pups, to reveal slow cycling stem cells, had BrdU within K8+ limbal basal cells and K8+ GCCs at the corneal periphery. By contrast, few bulbar conjunctival goblet cells retain BrdU label.
These data show that K8+ K12+ GCCs located at the corneal periphery in the unwounded mouse cornea contain corneal epithelial stem cells that give rise to corneal epithelial goblet cells. Also, we show that GCCs, and not conjunctival epithelial and/or goblet cells, migrate, proliferate, and expand on the ocular surface after wounds are made close to the limbus. We hypothesize that this expansion of GCCs, which we tentatively refer to as corneal goblet cell hyperplasia (CGH), may either co-exist with or be misdiagnosed as corneal epithelial stem cell deficiency (CESCD). These findings may have important implications for the treatment and diagnosis of CESCD.
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