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Woo-Kuen Lo, Sondip K. Biswas, Sumin Gu, Jean X. Jiang; Localized Alterations of Aquaporin Junctions and Connexin 50 Coincide with Cortical Cataract Formation in the Emory Mutant Mice. Invest. Ophthalmol. Vis. Sci. 2011;52(14):3410.
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The cleavage of C-terminus of aquaporin 0 can cause water channels to close and form aquaporin (square array) junctions whereas cleavage of C-terminus of connexin 50 can cause gap junction channels to remain opened. Here we evaluate the hypothesis that localized alterations of aquaporin junctions and Cx50 are associated with cortical cataract formation in the Emory mutant mice.
Lenses from Emory mutant and CFW wild-type mice between 2-12 months old were studied with SEM, freeze-fracture TEM, immunofluorescence and immunoblotting.
Lens opacities of various degrees were detected in superficial cortex of Emory mice between 7-12 months old. By SEM, undulating ridge surface patterns were regularly seen in normal deep cortical fibers (~600-1000 µm deep) of WT and Emory mice (with and without cataract). Unexpectedly, extensive ridge patterns were consistently present in superficial fibers (~200 µm deep) of the Emory cataracts, but not in the transparent Emory and WT lenses. These ridges were associated with disorganized, swollen or broken fiber cells. Freeze-fracture TEM showed that the ridges were composed of contiguous patches of square array particles (~7 nm in size) in the Emory mouse cataracts. However, gap junctions were seen in both superficial and deep cortical fibers in these lenses. By immunofluorescence, the Aqp0 C-terminus antibody showed the lack of labeling in the narrow zone (~150 µm) of superficial fibers in the Emory mouse cataracts as compared with the WT, suggesting premature cleavage of Aqp0 C-terminus in this region. Interestingly, the labeling of Cx50 C-terminus antibody was restricted only in the narrow zone (~10-50 µm) of superficial fibers in the Emory mouse cataracts. Immunoblotting confirmed that both C-termini of Aqp0 and Cx50 in the Emory mouse cataracts were significantly decreased to over 50% as compared to that of the WT.
This study reveals that the cortical cataract is apparently caused by disorganization and breakdown of superficial fibers in the Emory mutant mice. Abundant aquaporin junctions (i.e., closed water channels) are abnormally formed in these disorganized superficial fibers due to premature cleavage of Aqp0 C-terminus. Since Cx50 C-termini are also prematurely cleaved in superficial fibers, unregulated gap-junction channels are generated in the Emory mice. These two major changes would most likely cause disorganization and breakdown of superficial fibers in the Emory mutant mice.
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