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AV Ljubimov, NC Zorapapel, DJ Brown, MC Kenney; Aquaporins In Bullous Keratopathy Corneas . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1717.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A hallmark of pseudophakic bullous keratopathy (PBK) is extensive corneal edema. The current study was conducted to identify aquaporins (water channel proteins) expressed in PBK, keratoconus, and normal human corneas. Methods: Full-length cDNAs from PBK and age-matched normal corneas were hybridized to Clontech AtlasTM Human gene arrays (a total of 3,500 cDNA elements). Immunohistochemistry was performed with antibodies to aquaporin-0 (AQP-0), AQP-1, AQP-2, AQP-3, AQP-4, AQP-6, and AQP-9 on sections of 7 normal, 11 PBK and 5 keratoconus corneas. Stromal cell cultures from 5 normal and 5 PBK corneas were established and treated for 6 days with IGF-I, BMP-4, and TGF-ß2. Western blot analysis for AQP-1 was also performed. Results: Gene array analysis showed ≷ 4-fold increase of AQP-4 mRNA in PBK corneas compared to normal, which prompted us to study aquaporin expression in these corneas in more detail. In normal, keratoconus, and PBK corneas, AQP-1 was seen in stromal cells, AQP-3 and AQP-6, in the epithelial cells, and APQ-4, in the endothelial cells. The other AQPs were not found. PBK corneal epithelium had increased and more uniform staining for AQP-3 than normal corneal epithelium. AQP-4 appeared in the PBK corneal stroma, especially in areas of subepithelial fibrosis, in accordance with gene array data. Keratoconus corneas had normal AQP patterns. Cultured normal and PBK stromal cells treated with TGF-ß2 showed significant upregulation of AQP-1. Cultures treated with IGF-I or BMP-4 showed the same low levels of AQP-1 as did untreated cultures. Conclusion: PBK corneas contain significantly altered AQP patterns compared to normal or keratoconus corneas. TGF-ß2 can increase the expression of AQP-1 in corneal stromal cell cultures. The data suggest that AQP may play a role in corneal edema that is characteristic of PBK corneas.
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