Oxidative Stress, Lens Gap Junctions, and Cataracts

Overview

Journal Antioxid Redox Signal

Specialty Endocrinology

Date 2008 Oct 4

PMID 18831679

Citations 116

Authors

Viviana M Berthoud

Eric C Beyer

Affiliations

Soon will be listed here.

Abstract

The eye lens is constantly subjected to oxidative stress from radiation and other sources. The lens has several mechanisms to protect its components from oxidative stress and to maintain its redox state, including enzymatic pathways and high concentrations of ascorbate and reduced glutathione. With aging, accumulation of oxidized lens components and decreased efficiency of repair mechanisms can contribute to the development of lens opacities or cataracts. Maintenance of transparency and homeostasis of the avascular lens depend on an extensive network of gap junctions. Communication through gap junction channels allows intercellular passage of molecules (up to 1 kDa) including antioxidants. Lens gap junctions and their constituent proteins, connexins (Cx43, Cx46, and Cx50), are also subject to the effects of oxidative stress. These observations suggest that oxidative stress-induced damage to connexins (and consequent altered intercellular communication) may contribute to cataract formation.

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References

Pak J, Kim T, Kim M, Kim J, Choi H, Kim S . Reduced expression of 1-cys peroxiredoxin in oxidative stress-induced cataracts. Exp Eye Res. 2005; 82(5):899-906. DOI: 10.1016/j.exer.2005.10.017. View

Lin D, Shanks D, Prakash O, Takemoto D . Protein kinase C gamma mutations in the C1B domain cause caspase-3-linked apoptosis in lens epithelial cells through gap junctions. Exp Eye Res. 2007; 85(1):113-22. PMC: 2030616. DOI: 10.1016/j.exer.2007.03.007. View

Berry V, Mackay D, Khaliq S, Francis P, Hameed A, Anwar K . Connexin 50 mutation in a family with congenital "zonular nuclear" pulverulent cataract of Pakistani origin. Hum Genet. 1999; 105(1-2):168-70. DOI: 10.1007/s004399900094. View

Berthoud V, Westphale E, Grigoryeva A, Beyer E . PKC isoenzymes in the chicken lens and TPA-induced effects on intercellular communication. Invest Ophthalmol Vis Sci. 2000; 41(3):850-8. View

Vanita V, Singh J, Singh D, Varon R, Sperling K . A mutation in GJA8 (p.P88Q) is associated with "balloon-like" cataract with Y-sutural opacities in a family of Indian origin. Mol Vis. 2008; 14:1171-5. PMC: 2435161. View

Ho Y, Xiong Y, Ma W, Spector A, Ho D . Mice lacking catalase develop normally but show differential sensitivity to oxidant tissue injury. J Biol Chem. 2004; 279(31):32804-12. DOI: 10.1074/jbc.M404800200. View

Saleh S, Takemoto L, Zoukhri D, Takemoto D . PKC-gamma phosphorylation of connexin 46 in the lens cortex. Mol Vis. 2001; 7:240-6. View

Jiang H, Jin Y, Bu L, Zhang W, Liu J, Cui B . A novel mutation in GJA3 (connexin46) for autosomal dominant congenital nuclear pulverulent cataract. Mol Vis. 2003; 9:579-83. View

Yan M, Xiong C, Qing Ye S, Chen Y, Ke M, Zheng F . A novel connexin 50 (GJA8) mutation in a Chinese family with a dominant congenital pulverulent nuclear cataract. Mol Vis. 2008; 14:418-24. PMC: 2268715. View

10.

Mathias R, Rae J . The lens: local transport and global transparency. Exp Eye Res. 2004; 78(3):689-98. DOI: 10.1016/j.exer.2003.07.001. View

11.

Fleschner C . Connexin 46 and connexin 50 in selenite cataract. Ophthalmic Res. 2005; 38(1):24-8. DOI: 10.1159/000088527. View

12.

Inomata M, Hayashi M, Shumiya S, Kawashima S, Ito Y . Aminoguanidine-treatment results in the inhibition of lens opacification and calpain-mediated proteolysis in Shumiya cataract rats (SCR). J Biochem. 2000; 128(5):771-6. DOI: 10.1093/oxfordjournals.jbchem.a022814. View

13.

Shearer D, Ens W, Standing K, Valdimarsson G . Posttranslational modifications in lens fiber connexins identified by off-line-HPLC MALDI-quadrupole time-of-flight mass spectrometry. Invest Ophthalmol Vis Sci. 2008; 49(4):1553-62. DOI: 10.1167/iovs.07-1193. View

14.

Devi R, Vijayalakshmi P . Novel mutations in GJA8 associated with autosomal dominant congenital cataract and microcornea. Mol Vis. 2006; 12:190-5. View

15.

Yin X, Gu S, Jiang J . The development-associated cleavage of lens connexin 45.6 by caspase-3-like protease is regulated by casein kinase II-mediated phosphorylation. J Biol Chem. 2001; 276(37):34567-72. DOI: 10.1074/jbc.M106073200. View

16.

Lin D, Takemoto D . Oxidative activation of protein kinase Cgamma through the C1 domain. Effects on gap junctions. J Biol Chem. 2005; 280(14):13682-93. DOI: 10.1074/jbc.M407762200. View

17.

Behndig A, Karlsson K, Reaume A, Sentman M, Marklund S . In vitro photochemical cataract in mice lacking copper-zinc superoxide dismutase. Free Radic Biol Med. 2001; 31(6):738-44. DOI: 10.1016/s0891-5849(01)00651-7. View

18.

Mackay D, Ionides A, Kibar Z, Rouleau G, Berry V, Moore A . Connexin46 mutations in autosomal dominant congenital cataract. Am J Hum Genet. 1999; 64(5):1357-64. PMC: 1377871. DOI: 10.1086/302383. View

19.

Colombo B, Benedetti S, Ottolenghi S, Mora M, Pollo B, Poli G . The "bystander effect": association of U-87 cell death with ganciclovir-mediated apoptosis of nearby cells and lack of effect in athymic mice. Hum Gene Ther. 1995; 6(6):763-72. DOI: 10.1089/hum.1995.6.6-763. View

20.

Theiss C, Mazur A, Meller K, Mannherz H . Changes in gap junction organization and decreased coupling during induced apoptosis in lens epithelial and NIH-3T3 cells. Exp Cell Res. 2006; 313(1):38-52. DOI: 10.1016/j.yexcr.2006.09.029. View