Vision Science Program and School of Optometry, University of California, Berkeley, California, United States of America.
PLoS One. 2010 Sep 9;5(9):e12624. doi: 10.1371/journal.pone.0012624.
Cataracts, named for any opacity in the ocular lens, remain the leading cause of vision loss in the world. Non-surgical methods for cataract prevention are still elusive. We have genetically tested whether enhanced lens gap junction communication, provided by increased α3 connexin (Cx46) proteins expressed from α8(Kiα3) knock-in alleles in Gja8tm1(Gja3)Tww mice, could prevent nuclear cataracts caused by the γB-crystallin S11R mutation in CrygbS11R/S11R mice. Remarkably, homozygous knock-in α8(Kiα3/Kiα3) mice fully prevented nuclear cataracts, while single knock-in α8(Kiα3/-) allele mice showed variable suppression of nuclear opacities in CrygbS11R/S11R mutant mice. Cataract prevention was correlated with the suppression of many pathological processes, including crystallin degradation and fiber cell degeneration, as well as preservation of normal calcium levels and stable actin filaments in the lens. This work demonstrates that enhanced intercellular gap junction communication can effectively prevent or delay nuclear cataract formation and suggests that small metabolites transported through gap junction channels protect the stability of crystallin proteins and the cytoskeletal structures in the lens core. Thus, the use of an array of small molecules to promote lens homeostasis may become a feasible non-surgical approach for nuclear cataract prevention in the future.
白内障，得名于眼球晶状体的任何不透明，仍然是世界上导致视力丧失的主要原因。用于预防白内障的非手术方法仍难以捉摸。我们已经通过基因测试，研究了增强的晶状体缝隙连接通讯是否可以预防核性白内障，方法是通过增加α8(Kiα3)敲入等位基因在 Gja8tm1(Gja3)Tww 小鼠中表达的α3 连接蛋白（Cx46）来实现。令人惊讶的是，纯合敲入α8(Kiα3/Kiα3) 小鼠完全预防了核性白内障，而单敲入α8(Kiα3/-)等位基因小鼠在 CrygbS11R/S11R 突变小鼠中显示出核混浊程度的不同程度抑制。白内障预防与许多病理过程的抑制相关，包括晶状蛋白降解和纤维细胞退化，以及晶状体中正常钙水平和稳定的肌动蛋白丝的维持。这项工作表明，增强细胞间缝隙连接通讯可以有效预防或延迟核性白内障的形成，并表明通过缝隙连接通道运输的小分子代谢物可以保护晶状体核心中晶状蛋白和细胞骨架结构的稳定性。因此，未来使用一系列小分子来促进晶状体稳态可能成为预防核性白内障的可行非手术方法。
