Absence of α3 (Cx46) and α8 (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 α3 (Cx46) and α8 (Cx50) connexin subunits, to transport metabolites, secondary messages and ions between lens cells. To evaluate this hypothesis, we have generated α3(−/−) α8(−/−) double knockout mice and characterized their lens phenotypes. Without gap junctions between lens fiber cells, α3(−/−) α8(−/−) 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 α3(−/−) α8(−/−) lenses. However, a substantial reduction of γ-crystallin proteins, but not α- and β-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 γ-crystallin proteins and transcripts.