Xia Chun-hong, Cheng Catherine, Huang Qingling, Cheung Debra, Li Lin, Dunia Irene, Benedetti Lucio E, Horwitz Joseph, Gong Xiaohua
School of Optometry and Vision Science Program, University of California at Berkeley, 693 Minor Hall, Berkeley, CA 94720-2020, USA.
Exp Eye Res. 2006 Sep;83(3):688-96. doi: 10.1016/j.exer.2006.03.013. Epub 2006 May 11.
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.
晶状体的发育和透明度被认为依赖于细胞间缝隙连接通道，该通道由α3（Cx46）和α8（Cx50）连接蛋白亚基组成，用于在晶状体细胞之间运输代谢物、第二信使和离子。为了评估这一假设，我们培育了α3（-/-）α8（-/-）双敲除小鼠，并对其晶状体表型进行了表征。由于晶状体纤维细胞之间没有缝隙连接，α3（-/-）α8（-/-）晶状体出现了严重的白内障，这是由细胞肿胀和内部纤维变性引起的，而正常的周边纤维细胞在整个生命过程中持续形成。在α3（-/-）α8（-/-）晶状体中，既未发现降解的晶状体蛋白增加，也未发现水不溶性晶状体蛋白增加。然而，检测到γ-晶状体蛋白显著减少，但α-和β-晶状体蛋白未减少。这些结果表明，缝隙连接通讯对于维持内部纤维细胞的晶状体稳态很重要，缝隙连接的丧失会导致白内障形成以及γ-晶状体蛋白和转录本的减少。
