Advertisement

A Rat Eye Lens Model of Cataract Formation

  • Paul C. Guest
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1916)

Abstract

This chapter describes the use of lenses obtained from rats as a model of cataractogenesis. At the molecular level, this is visualized as reduced activity of oxidative reductive enzymes such as aldose reductase and increased proteolysis of lens structural proteins including vimentin. In this chapter, protocols for assessment of these two pathways are presented. Specifically, this analysis shows a comparison of aldose reductase activity and vimentin cleavage in male and female rat lenses. This is because female rats are more susceptible to cataract formation compared to males.

Key words

Diabetes Drug treatment Eye lens Aldose reductase Vimentin Proteolysis 

References

  1. 1.
    Bloemendal H, de Jong W, Jaenicke R, Lubsen NH, Slingsby C, Tardieu A (2004) Ageing and vision: structure, stability and function of lens crystallins. Prog Biophys Mol Biol 86:407–485CrossRefPubMedGoogle Scholar
  2. 2.
    Wistow G (2012) The human crystallin gene families. Hum Genomics 6:26.  https://doi.org/10.1186/1479-7364-6-26CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Hejtmancik JF, Kantorow M (2004) Molecular genetics of age-related cataract. Exp Eye Res 79:3–9CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Beebe DC, Holekamp NM, Shui YB (2010) Oxidative damage and the prevention of age-related cataracts. Ophthalmic Res 44:155–165CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Obrosova IG, Chung SS, Kador PF (2010) Diabetic cataracts: mechanisms and management. Diabetes Metab Res Rev 26:172–180CrossRefPubMedGoogle Scholar
  6. 6.
    Shearer TR, Shih M, Mizuno T, David LL (1996) Crystallins from rat lens are especially susceptible to calpain-induced light scattering compared to other species. Curr Eye Res 15:860–868CrossRefPubMedGoogle Scholar
  7. 7.
    Harrington V, Srivastava OP, Kirk M (2007) Proteomic analysis of water insoluble proteins from normal and cataractous human lenses. Mol Vis 13:1680–1694PubMedGoogle Scholar
  8. 8.
    Su SP, Song X, Xavier D, Aquilina JA (2015) Age-related cleavages of crystallins in human lens cortical fiber cells generate a plethora of endogenous peptides and high molecular weight complexes. Proteins 83:1878–1886CrossRefPubMedGoogle Scholar
  9. 9.
    Babizhayev MA (2011) Mitochondria induce oxidative stress, generation of reactive oxygen species and redox state unbalance of the eye lens leading to human cataract formation: disruption of redox lens organization by phospholipid hydroperoxides as a common basis for cataract disease. Cell Biochem Funct 29:183–206CrossRefPubMedGoogle Scholar
  10. 10.
    Babizhayev MA, Yegorov YE (2016) Reactive oxygen species and the aging eye: specific role of metabolically active mitochondria in maintaining lens function and in the initiation of the oxidation-induced maturity onset cataract—a novel platform of mitochondria-targeted antioxidants with broad therapeutic potential for redox regulation and detoxification of oxidants in eye diseases. Am J Ther 23:e98–e117.  https://doi.org/10.1097/MJT.0b013e3181ea31ffCrossRefPubMedGoogle Scholar
  11. 11.
    Su S, Leng F, Guan L, Zhang L, Ge J, Wang C et al (2014) Differential proteomic analyses of cataracts from rat models of type 1 and 2 diabetes. Invest Ophthalmol Vis Sci 55:7848–7861CrossRefPubMedGoogle Scholar
  12. 12.
    Miyazono Y, Harada K, Sugiyama K, Ueno M, Torii M, Kato I et al (2011) Toxicological characterization of N-methyl-N-nitrosourea-induced cataract in rats by LC/MS-based metabonomic analysis. J Appl Toxicol 31(7):655–662CrossRefPubMedGoogle Scholar
  13. 13.
    Nakano-Ito K, Fujikawa Y, Hihara T, Shinjo H, Kotani S, Suganuma A et al (2014) E2012-induced cataract and its predictive biomarkers. Toxicol Sci 137(1):249–258CrossRefPubMedGoogle Scholar
  14. 14.
    McColley SA (2016) A safety evaluation of ivacaftor for the treatment of cystic fibrosis. Expert Opin Drug Saf 15(5):709–715PubMedGoogle Scholar
  15. 15.
    Hiller R, Sperduto RD, Ederer F (1986) Epidemiologic associations with nuclear, cortical, and posterior subcapsular cataracts. Am J Epidemiol 124:916–925CrossRefPubMedGoogle Scholar
  16. 16.
    Hales AM, Chamberlain CG, Murphy CR, McAvoy JW (1997) Estrogen protects lenses against cataract induced by transforming growth factor-beta (TGFbeta). J Exp Med 185:273–280CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Guest PC, Skynner HA, Salim K, Tattersall FD, Knowles MR, Atack JR (2006) Detection of gender differences in rat lens proteins using 2-D-DIGE. Proteomics 6:667–676CrossRefPubMedGoogle Scholar
  18. 18.
    Ong EK, Suphioglu C, Singh MB, Knox RB (1990) Immunodetection methods for grass pollen allergens on western blots. Int Arch Allergy Appl Immunol 93(4):338–343CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Paul C. Guest
    • 1
  1. 1.Laboratory of Neuroproteomics, Department of Biochemistry and Tissue Biology, Institute of BiologyUniversity of Campinas (UNICAMP)CampinasBrazil

Personalised recommendations