Absence of alpha3 (Cx46) and alpha8 (Cx50) connexins leads to cataracts by affecting lens inner fiber cells

Lens development and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated alpha3(...

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Bibliographic Details
Published in:Experimental eye research 2006-09, Vol.83 (3), p.688-696
Main Authors: Xia, Chun-hong, Cheng, Catherine, Huang, Qingling, Cheung, Debra, Li, Lin, Dunia, Irene, Benedetti, Lucio E, Horwitz, Joseph, Gong, Xiaohua
Format: Article
Language:English
Subjects:
Animals
Cataract - pathology
Connexins - genetics
Connexins - physiology
Eye Proteins - genetics
Eye Proteins - physiology
Freeze Fracturing
gamma-Crystallins - genetics
gamma-Crystallins - metabolism
Gap Junctions - pathology
Lens, Crystalline - pathology
Mice
Mice, Knockout
Microscopy, Confocal
Reverse Transcriptase Polymerase Chain Reaction
Staining and Labeling
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Summary:Lens development and transparency have been hypothesized to depend on intercellular gap junction channels, consisting of alpha3 (Cx46) and alpha8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated alpha3(-/-) alpha8(-/-) double knockout mice and characterized their lens phenotypes. Without gap junctions between lens fiber cells, alpha3(-/-) alpha8(-/-) lenses displayed severe cataracts resulting from cell swelling and degeneration of inner fibers while normal peripheral fiber cells continued to form throughout life. Neither an increase of degraded crystallins nor an increase of water-insoluble crystallins was found in alpha3(-/-) alpha8(-/-) lenses. However, a substantial reduction of gamma-crystallin proteins, but not alpha- and beta-crystallins, was detected. These results suggest that gap junction communication is important for maintaining lens homeostasis of inner fiber cells and that a loss of gap junctions leads to cataract formation as well as reductions of gamma-crystallin proteins and transcripts.
ISSN:0014-4835