Aging-dependent loss of GAP junction proteins Cx46 and Cx50 in the fiber cells of human and mouse lenses accounts for the diminished coupling conductance

The homeostasis of the ocular lens is maintained by a microcirculation system propagated through gap junction channels. It is well established that the intercellular communications of the lens become deteriorative during aging. However, the molecular basis for this change in human lenses has not bee...

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Bibliographic Details
Published in:Aging (Albany, NY.) NY.), 2021-07, Vol.13 (13), p.17568-17591
Main Authors: Gong, Xiao-Dong, Wang, Yan, Hu, Xue-Bin, Zheng, Shu-Yu, Fu, Jia-Ling, Nie, Qian, Wang, Ling, Hou, Min, Xiang, Jia-Wen, Xiao, Yuan, Gao, Qian, Bai, Yue-Yue, Liu, Yi-Zhi, Li, David Wan-Cheng
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Aging - metabolism
Aging - pathology
Aging - physiology
Animals
Cataract - genetics
Cataract - pathology
Connexins - biosynthesis
Connexins - genetics
Epithelium, Corneal - pathology
Female
Gene Expression Regulation
Humans
Lens, Crystalline - pathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Middle Aged
Research Paper
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Summary:The homeostasis of the ocular lens is maintained by a microcirculation system propagated through gap junction channels. It is well established that the intercellular communications of the lens become deteriorative during aging. However, the molecular basis for this change in human lenses has not been well defined. Here, we present evidence to show that over 90% of Cx46 and Cx50 are lost in the fiber cells of normal human lenses aged 50 and above. From transparent to cataractous lenses, while Cx43 was upregulated, both Cx46 and Cx50 were significantly down-regulated in the lens epithelia. During aging of mouse lenses, Cx43 remained unchanged, but both Cx46 and Cx50 were significantly downregulated. Under oxidative stress treatment, mouse lenses develop cataractogenesis. Associated with this process, Cx43 was significantly upregulated, in contrast, Cx46 and Cx50 were sharply downregulated. Together, our results for the first time reveal that downregulation in Cx46 and Cx50 levels appears to be the major reason for the diminished coupling conductance, and the aging-dependent loss of Cx46 and Cx50 promotes senile cataractogenesis.
ISSN:1945-4589
1945-4589
DOI:10.18632/aging.203247