Abstract
Cataract is an opacification of the lens that results in obstruction of light and gradual loss of vision. It continues to be the leading cause of blindness worldwide despite the availability of effective surgery in developed countries. Primary cataract surgery is the most frequently performed surgical procedure in the world and remains the only cure. However, the surgical intervention is not without problems and can lead to a number of complications, the most common of which is secondary cataract, also known as posterior capsular opacification (PCO). The underlying causes of cataract are quite diverse with the majority acquired after middle age and referred to as “age related.” Congenital or juvenile cataracts, considered as “early-onset” cataracts, are less common but nonetheless have significant visual consequences. A number of risk factors have been identified that are associated with age-related cataracts, including diabetes, sunlight (ultraviolet light) exposure, smoking, steroid use, and oxygen exposure. Although studies in humans have provided important clues toward the potential causes of cataracts, elucidation of the mechanisms underlying cataractogenesis has only been possible through the use of experimental animal models. These models range from small animals such as mice, rats, chicks, and guinea pigs to larger mammals including rabbits, dogs, and primates. The goal of this chapter is to describe the experimental animal models most commonly utilized for investigating the genetic and environmental risk factors known to contribute to cataract formation. The strengths and weaknesses of each of these models are highlighted, as well as any recent advances.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Al-Ghoul KJ, Kirk T, Kuszak AJ, Zoltoski RK, Shiels A, Kuszak JR (2003) Lens structure in MIP-deficient mice. Anat Rec A Discov Mol Cell Evol Biol 273(2):714–730. doi:10.1002/ar.a.10080
Alizadeh A, Clark JI, Seeberger T, Hess J, Blankenship T, Spicer A, FitzGerald PG (2002) Targeted genomic deletion of the lens-specific intermediate filament protein CP49. Invest Ophthalmol Vis Sci 43(12):3722–3727
Allen PJ (2007) Cataract surgery practice and endophthalmitis prevention by Australian and New Zealand ophthalmologists—comment. Clin Exp Ophthalmol 35(4):391; author reply 391. doi:10.1111/j.1442-9071.2007.01497.x
Bantseev V, Oriowo OM, Giblin FJ, Leverenz VR, Trevithick JR, Sivak JG (2004) Effect of hyperbaric oxygen on guinea pig lens optical quality and on the refractive state of the eye. Exp Eye Res 78(5):925–931. doi:10.1016/j.exer.2004.01.002
Beby F, Commeaux C, Bozon M, Denis P, Edery P, Morle L (2007) New phenotype associated with an Arg116Cys mutation in the CRYAA gene: nuclear cataract, iris coloboma, and microphthalmia. Arch Ophthalmol 125(2):213–216. doi:10.1001/archopht.125.2.213
Beebe DC, Holekamp NM, Shui YB (2010a) Oxidative damage and the prevention of age-related cataracts. Ophthalm Res 44(3):155–165. doi:10.1159/000316481
Beebe DC, Shui Y-B, Holekamp NM (2010b) Biochemical mechanisms of age-related cataract. In: Levin LA, Albert DM (ed) Ocular diseases. Mechanisms and management. Elsevier Inc., Saunders
Berthoud VM, Beyer EC (2009) Oxidative stress, lens gap junctions, and cataracts. Antioxid Redox Signal 11(2):339–353. doi:10.1089/ars.2008.2119
Black RL, Oglesby RB, Von Sallmann L, Bunim JJ (1960) Posterior subcapsular cataracts induced by corticosteroids in patients with rheumatoid arthritis. JAMA 174:166–171
Bloemendal H, Zweers A, Vermorken F, Dunia I, Benedetti EL (1972) The plasma membranes of eye lens fibres. Biochemical and structural characterization. Cell Differ 1(2):91–106
Boyle DL, Takemoto L, Brady JP, Wawrousek EF (2003) Morphological characterization of the Alpha A- and Alpha B-crystallin double knockout mouse lens. BMC Ophthalmol 3:3
Brady JP, Garland D, Duglas-Tabor Y, Robison WG, Jr., Groome A, Wawrousek EF (1997) Targeted disruption of the mouse alpha A-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alpha B-crystallin. Proc Natl Acad Sci U S A 94(3):884–889
Brady JP, Garland DL, Green DE, Tamm ER, Giblin FJ, Wawrousek EF (2001) AlphaB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest Ophthalmol Vis Sci 42(12):2924–2934
Brakenhoff RH, Aarts HJ, Schuren F, Lubsen NH, Schoenmakers JG (1992) The second human beta B2-crystallin gene is a pseudogene. Exp Eye Res 54(5):803–806
Bullimore MA, Bailey IL (1993) Considerations in the subjective assessment of cataract. Optom Vis Sci: Official Publication Am Acad Optometry 70(11):880–885
Capetanaki Y, Smith S, Heath JP (1989) Overexpression of the vimentin gene in transgenic mice inhibits normal lens cell differentiation. J Cell Biol 109(4 Pt 1):1653–1664
Cartier M, Breitman ML, Tsui LC (1992) A frameshift mutation in the gamma E-crystallin gene of the Elo mouse. Nat Genetics 2(1):42–45. doi:10.1038/ng0992-42
Chambers C, Russell P (1991) Deletion mutation in an eye lens beta-crystallin. An animal model for inherited cataracts. J Biol Chem 266(11):6742–6746
Chandler HL, Haeussler DJ, Jr., Gemensky-Metzler AJ, Wilkie DA, Lutz EA (2012) Induction of posterior capsule opacification by hyaluronic acid in an ex vivo model. Invest Ophthalmol Vis Sci 53(4):1835–1845. doi:10.1167/iovs.11-8735
Chang B, Hawes NL, Smith RS, Heckenlively JR, Davisson MT, Roderick TH (1996) Chromosomal localization of a new mouse lens opacity gene (lop18). Genomics 36(1):171–173. doi:10.1006/geno.1996.0439
Cherfan GM, Michels RG, de Bustros S, Enger C, Glaser BM (1991) Nuclear sclerotic cataract after vitrectomy for idiopathic epiretinal membranes causing macular pucker. Am J Ophthalmol 111(4):434–438
Colucci-Guyon E, Portier MM, Dunia I, Paulin D, Pournin S, Babinet C (1994) Mice lacking vimentin develop and reproduce without an obvious phenotype. Cell 79(4):679–694
Coulombre AJ, Coulombre JL (1964) Lens development. I. Role of the lens in eye growth. J Exp Zoology 156:39–47
Davidson MG, Wormstone M, Morgan D, Malakof R, Allen J, McGahan MC (2000) Ex vivo canine lens capsular sac explants. Graefes Arch Clin Exp Ophthalmol 238(8):708–714
de Bustros S, Thompson JT, Michels RG, Enger C, Rice TA, Glaser BM (1988) Nuclear sclerosis after vitrectomy for idiopathic epiretinal membranes. Am J Ophthalmol 105(2):160–164
Delcourt C, Cristol JP, Tessier F, Leger CL, Michel F, Papoz L (2000) Risk factors for cortical, nuclear, and posterior subcapsular cataracts: the POLA study. Pathologies Oculaires Liees a l’Age. Am J Epidemiol 151(5):497–504
DeRosa AM, Xia CH, Gong X, White TW (2007) The cataract-inducing S50P mutation in Cx50 dominantly alters the channel gating of wild-type lens connexins. J Cell Sci 120(Pt 23):4107–4116. doi:10.1242/jcs.012237
DeRosa AM, Mese G, Li L, Sellitto C, Brink PR, Gong X, White TW (2009) The cataract causing Cx50-S50P mutant inhibits Cx43 and intercellular communication in the lens epithelium. Exp Cell Res 315(6):1063–1075. doi:10.1016/j.yexcr.2009.01.017
Devi RR, Yao W, Vijayalakshmi P, Sergeev YV, Sundaresan P, Hejtmancik JF (2008) Crystallin gene mutations in Indian families with inherited pediatric cataract. Mol Vis 14:1157–1170
Djabali K, de Nechaud B, Landon F, Portier MM (1997) AlphaB-crystallin interacts with intermediate filaments in response to stress. J Cell Sci 110(Pt 21):2759–2769
Ehling UH, Charles DJ, Favor J, Graw J, Kratochvilova J, Neuhauser-Klaus A, Pretsch W (1985) Induction of gene mutations in mice: the multiple endpoint approach. Mutation Res 150(1/2):393–401
Eshaghian J, Streeten BW (1980) Human posterior subcapsular cataract. An ultrastructural study of the posteriorly migrating cells. Arch Ophthalmol 98(1):134–143
FitzGerald PG (2009) Lens intermediate filaments. Exp Eye Res 88(2):165–172. doi:10.1016/j.exer.2008.11.007
Font R, Brownstein SA (1974) A light and electron microscopic study of anterior subcapsular cataracts. Am J Ophthalmol 78:972–984
Galichanin K, Lofgren S, Bergmanson J, Soderberg P (2010) Evolution of damage in the lens after in vivo close to threshold exposure to UV-B radiation: cytomorphological study of apoptosis. Exp Eye Res 91(3):369–377. doi:10.1016/j.exer.2010.06.009
Garner WH, Garner MH, Spector A (1981) Gamma-crystallin, a major cytoplasmic polypeptide disulfide linked to membrane proteins in human cataract. Biochem Biophys Res Commun 98(2):439–447
Gehlbach P, Hose S, Lei B, Zhang C, Cano M, Arora M, Neal R, Barnstable C, Goldberg MF, Zigler JS, Jr., Sinha D (2006) Developmental abnormalities in the Nuc1 rat retina: a spontaneous mutation that affects neuronal and vascular remodeling and retinal function. Neuroscience 137(2):447–461. doi:10.1016/j.neuroscience.2005.08.084
Giblin FJ (2000) Glutathione: a vital lens antioxidant. J Ocular Pharmacol Therapeut: Assoc Ocular Pharmacol Therapeut 16(2):121–135
Giblin FJ, Reddy VN (1980) Pyridine nucleotides in ocular tissues as determined by the cycling assay. Exp Eye Res 31(5):601–609
Giblin FJ, Padgaonkar VA, Leverenz VR, Lin LR, Lou MF, Unakar NJ, Dang L, Dickerson JE, Jr., Reddy VN (1995) Nuclear light scattering, disulfide formation and membrane damage in lenses of older guinea pigs treated with hyperbaric oxygen. Exp Eye Res 60(3):219–235
Giblin FJ, Leverenz VR, Padgaonkar VA, Unakar NJ, Dang L, Lin LR, Lou MF, Reddy VN, Borchman D, Dillon JP (2002) UVA light in vivo reaches the nucleus of the guinea pig lens and produces deleterious, oxidative effects. Exp Eye Res 75(4):445–458
Giblin FJ, Quiram PA, Leverenz VR, Baker RM, Dang L, Trese MT (2009) Enzyme-induced posterior vitreous detachment in the rat produces increased lens nuclear pO2 levels. Exp Eye Res 88(2):286–292. doi:10.1016/j.exer.2008.09.003
Giblin FJ, Lin LR, Simpanya MF, Leverenz VR, Fick CE (2012) A Class I UV-blocking (senofilcon A) soft contact lens prevents UVA-induced yellow fluorescence and NADH loss in the rabbit lens nucleus in vivo. Exp Eye Res 102:17–27. doi:10.1016/j.exer.2012.06.007
Glass AS, Dahm R (2004) The zebrafish as a model organism for eye development. Ophthal Res 36(1):4–24. doi:10.1159/000076105
Goishi K, Shimizu A, Najarro G, Watanabe S, Rogers R, Zon LI, Klagsbrun M (2006) AlphaA-crystallin expression prevents gamma-crystallin insolubility and cataract formation in the zebrafish cloche mutant lens. Development 133(13):2585–2593. doi:10.1242/dev.02424
Gong X, Li E, Klier G, Huang Q, Wu Y, Lei H, Kumar NM, Horwitz J, Gilula NB (1997) Disruption of alpha3 connexin gene leads to proteolysis and cataractogenesis in mice. Cell 91(6):833–843
Gong X, Agopian K, Kumar NM, Gilula NB (1999) Genetic factors influence cataract formation in alpha 3 connexin knockout mice. Dev Gen 24(1/2):27–32. doi:10.1002/(SICI)1520-6408(1999)24:1/2<27::AID-DVG4>3.0.CO;2–7
Goodenough DA (1992) The crystalline lens. A system networked by gap junctional intercellular communication. Seminars Cell Biol 3(1):49–58
Gorin MB, Yancey SB, Cline J, Revel JP, Horwitz J (1984) The major intrinsic protein (MIP) of the bovine lens fiber membrane: characterization and structure based on cDNA cloning. Cell 39(1):49–59
Gosselin ME, Kapustij CJ, Venkateswaran UD, Leverenz VR, Giblin FJ (2007) Raman spectroscopic evidence for nuclear disulfide in isolated lenses of hyperbaric oxygen-treated guinea pigs. Exp Eye Res 84(3):493–499. doi:10.1016/j.exer.2006.11.002
Graw J (1997) The crystallins: genes, proteins and diseases. Biol Chem 378(11):1331–1348
Graw J (2009) Genetics of crystallins: cataract and beyond. Exp Eye Res 88(2):173–189. doi:10.1016/j.exer.2008.10.011
Graw J, Jung M, Loster J, Klopp N, Soewarto D, Fella C, Fuchs H, Reis A, Wolf E, Balling R, Hrabe de Angelis M (1999) Mutation in the betaA3/A1-crystallin encoding gene Cryba1 causes a dominant cataract in the mouse. Genomics 62(1):67–73. doi:10.1006/geno.1999.5974
Graw J, Klopp N, Illig T, Preising MN, Lorenz B (2006) Congenital cataract and macular hypoplasia in humans associated with a de novo mutation in CRYAA and compound heterozygous mutations in P. Graefes Arch Clin Exp Ophthalmol 244(8):912–919. doi:10.1007/s00417-005-0234-x
Graw J, Loster J, Soewarto D, Fuchs H, Meyer B, Reis A, Wolf E, Balling R, Hrabe de Angelis M (2001) Characterization of a new, dominant V124E mutation in the mouse alphaA-crystallin-encoding gene. Invest Ophthalmol Vis Sci 42(12):2909–2915
Gu F, Luo W, Li X, Wang Z, Lu S, Zhang M, Zhao B, Zhu S, Feng S, Yan YB, Huang S, Ma X (2008) A novel mutation in AlphaA-crystallin (CRYAA) caused autosomal dominant congenital cataract in a large Chinese family. Human Mutat 29(5):769. doi:10.1002/humu.20724
Gupta V, Wagner BJ (2009) Search for a functional glucocorticoid receptor in the mammalian lens. Exp Eye Res 88(2):248–256. doi:10.1016/j.exer.2008.04.003
Gwon A (2006) Lens regeneration in mammals: a review. Surv Ophthalmol 51(1):51–62. doi:10.1016/j.survophthal.2005.11.005
Gwon A (2008) The rabbit in cataract/IOL surgery. In: Tsonis P (ed) Animal models in eye research. Elsevier, New York
Halder N, Joshi S, Gupta SK (2003) Lens aldose reductase inhibiting potential of some indigenous plants. J Ethnopharmacol 86(1):113–116
Hales AM, Schulz MW, Chamberlain CG, McAvoy JW (1994) TGF-beta 1 induces lens cells to accumulate alpha-smooth muscle actin, a marker for subcapsular cataracts. Curr Eye Res 13(12):885–890
Hansen L, Yao W, Eiberg H, Kjaer KW, Baggesen K, Hejtmancik JF, Rosenberg T (2007) Genetic heterogeneity in microcornea-cataract: five novel mutations in CRYAA, CRYGD, and GJA8. Invest Ophthalmol Vis Sci 48(9):3937–3944. doi:10.1167/iovs.07-0013
Hatters DM, Lindner RA, Carver JA, Howlett GJ (2001) The molecular chaperone, alpha-crystallin, inhibits amyloid formation by apolipoprotein C-II. J Biol Chem 276(36):33755–33761. doi:10.1074/jbc.M105285200
Hegde KR, Henein MG, Varma SD (2003) Establishment of mouse as an animal model for study of diabetic cataracts: biochemical studies. Diabetes Obes Metab 5(2):113–119
Hejtmancik JF (2008) Congenital cataracts and their molecular genetics. Seminars Cell Dev Biol 19(2):134–149. doi:10.1016/j.semcdb.2007.10.003
Horwitz J (2003) Alpha-crystallin. Exp Eye Res 76(2):145–153
Kador PF, Fukui HN, Fukushi S, Jernigan HM, Jr., Kinoshita JH (1980) Philly mouse: a new model of hereditary cataract. Exp Eye Res 30(1):59–68
Kador PF, Sun G, Rait VK, Rodriguez L, Ma Y, Sugiyama K (2001) Intrinsic inhibition of aldose reductase. J Ocul Pharmacol Ther: The Official J Assoc Ocular Pharmacol Therapeutics 17(4):373–381. doi:10.1089/108076801753162780
Kador PF, Betts D, Wyman M, Blessing K, Randazzo J (2006) Effects of topical administration of an aldose reductase inhibitor on cataract formation in dogs fed a diet high in galactose. Am J Veterinary Res 67(10):1783–1787. doi:10.2460/ajvr.67.10.1783
Kappelhof JP, Vrensen GF (1992) The pathology of after-cataract. A minireview. Acta Ophthalmol Suppl (205):13–24
Khan AO, Aldahmesh MA, Meyer B (2007) Recessive congenital total cataract with microcornea and heterozygote carrier signs caused by a novel missense CRYAA mutation (R54C). Am J Ophthalmol 144(6):949–952. doi:10.1016/j.ajo.2007.08.005
Kronschlager M, Lofgren S, Yu Z, Talebizadeh N, Varma SD, Soderberg P (2013) Caffeine eye drops protect against UV-B cataract. Exp Eye Res 113:26–31. doi:10.1016/j.exer.2013.04.015
Lassen N, Bateman JB, Estey T, Kuszak JR, Nees DW, Piatigorsky J, Duester G, Day BJ, Huang J, Hines LM, Vasiliou V (2007) Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(−/−)/Aldh1a1(−/−) knock-out mice. J Biol Chem 282(35):25668–25676. doi:10.1074/jbc.M702076200
Lee AY, Chung SK, Chung SS (1995) Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens. Proc Natl Acad Sci U S A 92(7):2780–2784
Lee KW, Meyer N, Ortwerth BJ (1999) Chromatographic comparison of the UVA sensitizers present in brunescent cataracts and in calf lens proteins ascorbylated in vitro. Exp Eye Res 69(4):375–384. doi:10.1006/exer.1999.0709
Li XQ, Cai HC, Zhou SY, Yang JH, Xi YB, Gao XB, Zhao WJ, Li P, Zhao GY, Tong Y, Bao FC, Ma Y, Wang S, Yan YB, Lu CL, Ma X (2012) A novel mutation impairing the tertiary structure and stability of gammaC-crystallin (CRYGC) leads to cataract formation in humans and zebrafish lens. Hum Mutat 33(2):391–401. doi:10.1002/humu.21648
Li Q, Yan H, Ding TB, Han J, Shui YB, Beebe DC (2013) Oxidative responses induced by pharmacologic vitreolysis and/or long-term hyperoxia treatment in rat lenses. Curr Eye Res 38(6):639–648. doi:10.3109/02713683.2012.760741
Litt M, Kramer P, LaMorticella DM, Murphey W, Lovrien EW, Weleber RG (1998) Autosomal dominant congenital cataract associated with a missense mutation in the human alpha crystallin gene CRYAA. Hum Mol Genet 7(3):471–474
Liu J, Hales AM, Chamberlain CG, McAvoy JW (1994) Induction of cataract-like changes in rat lens epithelial explants by transforming growth factor beta. Invest Ophthalmol Vis Sci 35(2):388–401
Lou MF (2003) Redox regulation in the lens. Prog Retin Eye Res 22(5):657–682
Lyu J, Kim JA, Chung SK, Kim KS, Joo CK (2003) Alteration of cadherin in dexamethasone-induced cataract organ-cultured rat lens. Invest Ophthalmol Vis Sci 44(5):2034–2040
Mackay DS, Andley UP, Shiels A (2003) Cell death triggered by a novel mutation in the alphaA-crystallin gene underlies autosomal dominant cataract linked to chromosome 21q. Eur J Hum Genet: EJHG 11(10):784–793. doi:10.1038/sj.ejhg.5201046
Malicki J (2000) Genetic analysis of eye development in zebrafish. Results Probl Cell Differ 31:257–282
Mansfield KJ, Cerra A, Chamberlain CG (2004) FGF-2 counteracts loss of TGFbeta affected cells from rat lens explants: implications for PCO (after cataract). Mol Vis 10:521–532
Manthey AL, Terrell AM, Wang Y, Taube JR, Yallowitz AR, Duncan MK (2014) The Zeb proteins deltaEF1 and Sip1 may have distinct functions in lens cells following cataract surgery. Invest Ophthalmol Vis Sci 55(8):5445–5455. doi:10.1167/iovs.14-14845
Martinez-Wittinghan FJ, Sellitto C, Li L, Gong X, Brink PR, Mathias RT, White TW (2003) Dominant cataracts result from incongruous mixing of wild-type lens connexins. J Cell Biol 161(5):969–978. doi:10.1083/jcb.200303068
Maruoka S, Matsuura T, Kawasaki K, Okamoto M, Yoshiaki H, Kodama M, Sugiyama M, Annaka M (2006) Biocompatibility of polyvinylalcohol gel as a vitreous substitute. Curr Eye Res 31(7–8):599–606. doi:10.1080/02713680600813854
Mathias RT, White TW, Gong X (2010) Lens gap junctions in growth, differentiation, and homeostasis. Physiol Rev 90(1):179–206. doi:10.1152/physrev.00034.2009
Matsuura T, Yamagishi S, Kodama Y, Shibata R, Ueda S, Narama I (2005) Otsuka Long-Evans Tokushima fatty (OLETF) rat is not a suitable animal model for the study of angiopathic diabetic retinopathy. Int J Tissue Reactions 27(2):59–62
McCarty CA, Taylor HR (2002) A review of the epidemiologic evidence linking ultraviolet radiation and cataracts. Dev Ophthalmol 35:21–31
Meehan S, Berry Y, Luisi B, Dobson CM, Carver JA, MacPhee CE (2004) Amyloid fibril formation by lens crystallin proteins and its implications for cataract formation. J Biol Chem 279(5):3413–3419. doi:10.1074/jbc.M308203200
Merriam JC, Lofgren S, Michael R, Soderberg P, Dillon J, Zheng L, Ayala M (2000) An action spectrum for UV-B radiation and the rat lens. Invest Ophthalmol Vis Sci 41(9):2642–2647
Meyer LM, Lofgren S, Ho YS, Lou M, Wegener A, Holz F, Soderberg P (2009) Absence of glutaredoxin1 increases lens susceptibility to oxidative stress induced by UVR-B. Exp Eye Res 89(6):833–839. doi:10.1016/j.exer.2009.07.020
Michael R, Vrensen GF, van Marle J, Gan L, Soderberg PG (1998) Apoptosis in the rat lens after in vivo threshold dose ultraviolet irradiation. Invest Ophthalmol Vis Sci 39(13):2681–2687
Moghaddam MS, Kumar PA, Reddy GB, Ghole VS (2005) Effect of Diabecon on sugar-induced lens opacity in organ culture: mechanism of action. J Ethnopharmacol 97(2):397–403. doi:10.1016/j.jep.2004.11.032
Moreau KL, King JA (2012) Protein misfolding and aggregation in cataract disease and prospects for prevention. Trends Mol Med 18(5):273–282. doi:10.1016/j.molmed.2012.03.005
Mori Y, Yokoyama J, Nishimura M, Oka H, Mochio S, Ikeda Y (1992) Development of diabetic complications in a new diabetic strain of rat (WBN/Kob). Pancreas 7(5):569–577
Mörner CT (1894) Untersuchungen der Protein substanzen in den lichtbrechenden medien des Auges. Hoppe Seyler Z Physiol Chem 18(61)
Mou L, Xu JY, Li W, Lei X, Wu Y, Xu G, Kong X, Xu GT (2010) Identification of vimentin as a novel target of HSF4 in lens development and cataract by proteomic analysis. Invest Ophthalmol Vis Sci 51(1):396–404. doi:10.1167/iovs.09-3772
Nakamura M, Russell P, Carper DA, Inana G, Kinoshita JH (1988) Alteration of a developmentally regulated, heat-stable polypeptide in the lens of the Philly mouse. Implications for cataract formation. J Biol Chem 263(35):19218–19221
Nicholl ID, Quinlan RA (1994) Chaperone activity of alpha-crystallins modulates intermediate filament assembly. EMBO J 13(4):945–953
Novotny GE, Pau H (1984) Myofibroblast-like cells in human anterior capsular cataract. Virchows Archiv A. Pathological Anatomy Histopathol 404(4):393–401
Obrosova IG, Chung SS, Kador PF (2010) Diabetic cataracts: mechanisms and management. Diabetes/Metabolism Res Rev 26(3):172–180. doi:10.1002/dmrr.1075
Okamura T, Miyoshi I, Takahashi K, Mototani Y, Ishigaki S, Kon Y, Kasai N (2003) Bilateral congenital cataracts result from a gain-of-function mutation in the gene for aquaporin-0 in mice. Genomics 81(4):361–368
Oriowo OM, Cullen AP, Chou BR, Sivak JG (2001) Action spectrum and recovery for in vitro UV-induced cataract using whole lenses. Invest Ophthalmol Vis Sci 42(11):2596–2602
Ostenson CG, Efendic S (2007) Islet gene expression and function in type 2 diabetes; studies in the Goto-Kakizaki rat and humans. Diabetes, Obes Metab 9(Suppl 2):180–186. doi:10.1111/j.1463-1326.2007.00787.x
Palmquist BM, Philipson B, Barr PO (1984) Nuclear cataract and myopia during hyperbaric oxygen therapy. Br J Ophthalmol 68 (2):113–117
Parker NR, Jamie JF, Davies MJ, Truscott RJ (2004) Protein-bound kynurenine is a photosensitizer of oxidative damage. Free Radical Biology Med 37 (9):1479–1489. doi:10.1016/j.freeradbiomed.2004.07.015
Parthasarathy G, Ma B, Zhang C, Gongora C, Samuel Zigler J, Jr., Duncan MK, Sinha D (2011) Expression of betaA3/A1-crystallin in the developing and adult rat eye. J Mol Histol 42(1):59–69. doi:10.1007/s10735-010-9307-1
Pei C, Xu Y, Jiang JX, Cui LJ, Li L, Qin L (2013) Application of sustained delivery microsphere of cyclosporine A for preventing posterior capsular opacification in rabbits. IntJ Ophthalmol 6(1):1–7. doi:10.3980/j.issn.2222-3959.2013.01.01
Pitts DG (1978) Glenn A. Fry Award Lecture–1977. The ocular effects of ultraviolet radiation. Am J Optomet Physiol Optics 55(1):19–35
Pollreisz A, Schmidt-Erfurth U (2010) Diabetic cataract-pathogenesis, epidemiology and treatment. J Ophthalmol 2010:608751. doi:10.1155/2010/608751
Posner M (2003) A comparative view of alpha crystallins: the contribution of comparative studies to understanding function. Integr Comp Biol 43(4):481–491. doi:10.1093/icb/43.4.481
Pot SA, Chandler HL, Colitz CM, Bentley E, Dubielzig RR, Mosley TS, Reid TW, Murphy CJ (2009) Selenium functionalized intraocular lenses inhibit posterior capsule opacification in an ex vivo canine lens capsular bag assay. Exp Eye Res 89(5):728–734. doi:10.1016/j.exer.2009.06.016
Pras E, Frydman M, Levy-Nissenbaum E, Bakhan T, Raz J, Assia EI, Goldman B, Pras E (2000) A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family. Invest Ophthalmol Vis Sci 41(11):3511–3515
Quiram PA, Leverenz VR, Baker RM, Dang L, Giblin FJ, Trese MT (2007) Microplasmin-induced posterior vitreous detachment affects vitreous oxygen levels. Retina 27(8):1090–1096. doi:10.1097/IAE.0b013e3180654229
Ramaekers FC, Osborn M, Schimid E, Weber K, Bloemendal H, Franke WW (1980) Identification of the cytoskeletal proteins in lens-forming cells, a special epitheloid cell type. Exp Cell Res 127(2):309–327
Rao PV, Zigler JS, Jr. (1990) Extremely high levels of NADPH in guinea pig lens: correlation with zeta-crystallin concentration. Biochem Biophys Res Commun 167(3):1221–1228
Reddy MA, Francis PJ, Berry V, Bhattacharya SS, Moore AT (2004) Molecular genetic basis of inherited cataract and associated phenotypes. Surv Ophthalmol 49(3):300–315. doi:10.1016/j.survophthal.2004.02.013
Richter L, Flodman P, Barria von-Bischhoffshausen F, Burch D, Brown S, Nguyen L, Turner J, Spence MA, Bateman JB (2008) Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA). Am J Med Gen Part A 146A (7):833–842. doi:10.1002/ajmg.a.32236
Robertson JV, Nathu Z, Najjar A, Dwivedi D, Gauldie J, West-Mays JA (2007) Adenoviral gene transfer of bioactive TGFbeta1 to the rodent eye as a novel model for anterior subcapsular cataract. Mol Vis 13:457–469
Rong P, Wang X, Niesman I, Wu Y, Benedetti LE, Dunia I, Levy E, Gong X (2002) Disruption of Gja8 (alpha8 connexin) in mice leads to microphthalmia associated with retardation of lens growth and lens fiber maturation. Development 129(1):167–174
Rubinos C, Villone K, Mhaske PV, White TW, Srinivas M (2014) Functional effects of Cx50 mutations associated with congenital cataracts. Am J Physiol Cell Physiol 306(3):C212–220. doi:10.1152/ajpcell.00098.2013
Sandilands A, Hutcheson AM, Long HA, Prescott AR, Vrensen G, Loster J, Klopp N, Lutz RB, Graw J, Masaki S, Dobson CM, MacPhee CE, Quinlan RA (2002) Altered aggregation properties of mutant gamma-crystallins cause inherited cataract. EMBO J 21(22):6005–6014
Sandilands A, Prescott AR, Wegener A, Zoltoski RK, Hutcheson AM, Masaki S, Kuszak JR, Quinlan RA (2003) Knockout of the intermediate filament protein CP49 destabilises the lens fibre cell cytoskeleton and decreases lens optical quality, but does not induce cataract. Exp Eye Res 76(3):385–391
Santhiya ST, Soker T, Klopp N, Illig T, Prakash MV, Selvaraj B, Gopinath PM, Graw J (2006) Identification of a novel, putative cataract-causing allele in CRYAA (G98R) in an Indian family. Mol Vis 12:768–773
Sasase T, Ohta T, Masuyama T, Yokoi N, Kakehashi A, Shinohara M (2013) The spontaneously diabetic torii rat: an animal model of nonobese type 2 diabetes with severe diabetic complications. J Diabetes Res 2013:976209. doi:10.1155/2013/976209
Saxby L, Rosen E, Boulton M (1998) Lens epithelial cell proliferation, migration, and metaplasia following capsulorhexis. Br J Ophthalmol 82(8):945–952
Schaumberg DA, Dana MR, Christen WG, Glynn RJ (1998) A systematic overview of the incidence of posterior capsule opacification. Ophthalmology 105(7):1213–1221. doi:10.1016/S0161-6420(98)97023-3
Schmidt RE, Dorsey DA, Beaudet LN, Peterson RG (2003) Analysis of the Zucker Diabetic Fatty (ZDF) type 2 diabetic rat model suggests a neurotrophic role for insulin/IGF-I in diabetic autonomic neuropathy. Am J Pathol 163(1):21–28. doi:10.1016/S0002-9440(10)63626-7
Shiels A, Bassnett S (1996) Mutations in the founder of the MIP gene family underlie cataract development in the mouse. Nat Genet 12(2):212–215. doi:10.1038/ng0296-212
Shiels A, Hejtmancik JF (2007) Genetic origins of cataract. Arch Ophthalmol 125(2):165–173. doi:10.1001/archopht.125.2.165
Shiels A, Mackay D, Ionides A, Berry V, Moore A, Bhattacharya S (1998) A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant “zonular pulverulent” cataract, on chromosome 1q. Am J Hum Genet 62(3):526–532. doi:10.1086/301762
Shiels A, Bassnett S, Varadaraj K, Mathias R, Al-Ghoul K, Kuszak J, Donoviel D, Lilleberg S, Friedrich G, Zambrowicz B (2001) Optical dysfunction of the crystalline lens in aquaporin-0-deficient mice. Physiol Genom 7(2):179–186. doi:10.1152/physiolgenomics.00078.2001
Sidjanin DJ, Parker-Wilson DM, Neuhauser-Klaus A, Pretsch W, Favor J, Deen PM, Ohtaka-Maruyama C, Lu Y, Bragin A, Skach WR, Chepelinsky AB, Grimes PA, Stambolian DE (2001) A 76-bp deletion in the Mip gene causes autosomal dominant cataract in Hfi mice. Genomics 74(3):313–319. doi:10.1006/geno.2001.6509
Simpanya MF, Ansari RR, Leverenz V, Giblin FJ (2008) Measurement of lens protein aggregation in vivo using dynamic light scattering in a guinea pig/UVA model for nuclear cataract. Photochem Photobiol 84(6):1589–1595. doi:10.1111/j.1751-1097.2008.00390.x
Sinha D, Hose S, Zhang C, Neal R, Ghosh M, O'Brien TP, Sundin O, Goldberg MF, Robison WG, Jr., Russell P, Lo WK, Samuel Zigler J, Jr. (2005) A spontaneous mutation affects programmed cell death during development of the rat eye. Exp Eye Res 80(3):323–335. doi:10.1016/j.exer.2004.09.014
Sinha D, Klise A, Sergeev Y, Hose S, Bhutto IA, Hackler L, Jr., Malpic-Llanos T, Samtani S, Grebe R, Goldberg MF, Hejtmancik JF, Nath A, Zack DJ, Fariss RN, McLeod DS, Sundin O, Broman KW, Lutty GA, Zigler JS, Jr. (2008) betaA3/A1-crystallin in astroglial cells regulates retinal vascular remodeling during development. Molecular Cell Neurosci 37(1):85–95. doi:10.1016/j.mcn.2007.08.016
Soderberg PG (1990) Experimental cataract induced by ultraviolet radiation. Acta Ophthalmol Suppl (196):1–75
Soderberg PG, Lofgren S, Ayala M, Dong X, Kakar M, Mody V (2002) Toxicity of ultraviolet radiation exposure to the lens expressed by maximum tolerable dose. Dev Ophthalmol 35:70–75
Spector A, Huang RR, Wang GM (1985) The effect of H2O2 on lens epithelial cell glutathione. Curr Eye Res 4(12):1289–1295
Srinivasan Y, Lovicu FJ, Overbeek PA (1998) Lens-specific expression of transforming growth factor beta1 in transgenic mice causes anterior subcapsular cataracts. J Clin Invest 101(3):625–634. doi:10.1172/JCI1360
Stanga PE, Boyd SR, Hamilton AM (1999) Ocular manifestations of diabetes mellitus. Curr Opin Ophthalmol 10(6):483–489
Swindle-Reilly KE, Shah M, Hamilton PD, Eskin TA, Kaushal S, Ravi N (2009) Rabbit study of an in situ forming hydrogel vitreous substitute. Invest Ophthalmol Vis Sci 50(10):4840–4846. doi:10.1167/iovs.08-2891
Talbot WS, Hopkins N (2000) Zebrafish mutations and functional analysis of the vertebrate genome. Genes Dev 14(7):755–762
Taylor HR (1980) The environment and the lens. Br J Ophthalmol 64(5):303–310
Thisse C, Zon LI (2002) Organogenesis–heart and blood formation from the zebrafish point of view. Science 295(5554):457–462. doi:10.1126/science.1063654
Thompson JT, Glaser BM, Sjaarda RN, Murphy RP (1995) Progression of nuclear sclerosis and long-term visual results of vitrectomy with transforming growth factor beta-2 for macular holes. Am J Ophthalmol 119(1):48–54
Ueda Y, Duncan MK, David LL (2002) Lens proteomics: the accumulation of crystallin modifications in the mouse lens with age. Invest Ophthalmol Vis Sci 43(1):205–215
Vanita V, Singh JR, Hejtmancik JF, Nuernberg P, Hennies HC, Singh D, Sperling K (2006) A novel fan-shaped cataract-microcornea syndrome caused by a mutation of CRYAA in an Indian family. Mol Vis 12:518–522
Varma SD, Kinoshita JH (1974) The absence of cataracts in mice with congenital hyperglycemia. Exp Eye Res 19(6):577–582
Varma SD, Hegde KR, Kovtun S (2008) UV-B-induced damage to the lens in vitro: prevention by caffeine. J Ocul Pharmacol Ther: the official J Assoc Ocular Pharmacol Therapeutics 24(5):439–444. doi:10.1089/jop.2008.0035
Walker JL, Wolff IM, Zhang L, Menko AS (2007) Activation of SRC kinases signals induction of posterior capsule opacification. Invest Ophthalmol Vis Sci 48(5):2214–2223. doi:10.1167/iovs.06-1059
Wallentin N, Wickstrom K, Lundberg C (1998) Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell proliferation. Invest Ophthalmol Vis Sci 39(8):1410–1418
Wang J, Lofgren S, Dong X, Galichanin K, Soderberg PG (2010) Evolution of light scattering and redox balance in the rat lens after in vivo exposure to close-to-threshold dose ultraviolet radiation. Acta Ophthalmologica 88(7):779–785. doi:10.1111/j.1755-3768.2009.01826.x
Wang C, Dawes LJ, Liu Y, Wen L, Lovicu FJ, McAvoy JW (2013) Dexamethasone influences FGF-induced responses in lens epithelial explants and promotes the posterior capsule coverage that is a feature of glucocorticoid-induced cataract. Exp Eye Res 111:79–87. doi:10.1016/j.exer.2013.03.006
Watanabe H, Kosano H, Nishigori H (2000) Steroid-induced short term diabetes in chick embryo: reversible effects of insulin on metabolic changes and cataract formation. Invest Ophthalmol Vis Sci 41(7):1846–1852
Watanabe K, Wada K, Ohashi T, Okubo S, Takekuma K, Hashizume R, Hayashi J, Serikawa T, Kuramoto T, Kikkawa Y (2012) A 5-bp insertion in Mip causes recessive congenital cataract in KFRS4/Kyo rats. PloS ONE 7(11):e50737. doi:10.1371/journal.pone.0050737
West-Mays JA, Sheardown H (2010) Posterior capsule opacification. In: Levin LA, Albert DM (ed) Ocular diseases. Mechanisms and management. Elsevier Inc., Saunders
West-Mays JA, Pino G, Lovicu FJ (2010) Development and use of the lens epithelial explant system to study lens differentiation and cataractogenesis. Prog Retin Eye Res 29(2):135–143. doi:10.1016/j.preteyeres.2009.12.001
White TW (2002) Unique and redundant connexin contributions to lens development. Science 295(5553):319–320. doi:10.1126/science.1067582
White TW, Goodenough DA, Paul DL (1998) Targeted ablation of connexin50 in mice results in microphthalmia and zonular pulverulent cataracts. J Cell Biol 143(3):815–825
WHO (1998) Ageing: a public health challenge. http://www.who.int/mediacentre/factsheets/fs135/en/.
WHO (2000) Blindness: Vision 2020—The Global Initiative for the Elimination of Avoidable Blindness. http://www.who.int/mediacentre/factsheets/fs213/en/.
WHO (2012) Visual impairment and blindness. http://www.who.int/mediacentre/factsheets/fs282/en/index.html.
Wood AM, Truscott RJ (1994) Ultraviolet filter compounds in human lenses: 3-hydroxykynurenine glucoside formation. Vis Res 34(11):1369–1374
Wormstone IM (2002) Posterior capsule opacification: a cell biological perspective. Exp Eye Res 74(3):337–347. doi:10.1006/exer.2001.1153
Wormstone IM, Liu CS, Rakic JM, Marcantonio JM, Vrensen GF, Duncan G (1997) Human lens epithelial cell proliferation in a protein-free medium. Invest Ophthalmol Vis Sci 38(2):396–404
Wormstone IM, Wang L, Liu CS (2009) Posterior capsule opacification. Exp Eye Res 88(2):257–269. doi:10.1016/j.exer.2008.10.016
Wu JW, Chen ME, Wen WS, Chen WA, Li CT, Chang CK, Lo CH, Liu HS, Wang SS (2014) Comparative analysis of human gammaD-crystallin aggregation under physiological and low pH conditions. PloS ONE 9(11):e112309. doi:10.1371/journal.pone.0112309
Xia CH, Cheung D, DeRosa AM, Chang B, Lo WK, White TW, Gong X (2006a) Knock-in of alpha3 connexin prevents severe cataracts caused by an alpha8 point mutation. J Cell Sci 119(Pt 10):2138–2144. doi:10.1242/jcs.02940
Xia CH, Liu H, Chang B, Cheng C, Cheung D, Wang M, Huang Q, Horwitz J, Gong X (2006b) Arginine 54 and Tyrosine 118 residues of {alpha}A-crystallin are crucial for lens formation and transparency. Invest Ophthalmol Vis Sci 47(7):3004–3010. doi:10.1167/iovs.06-0178
Xia CH, Chang B, Derosa AM, Cheng C, White TW, Gong X (2012) Cataracts and microphthalmia caused by a Gja8 mutation in extracellular loop 2. PLoS ONE 7(12):e52894. doi:10.1371/journal.pone.0052894
Zeiss CJ (2013) Translational models of ocular disease. Veterinary Ophthalmol 16(Suppl 1):15–33. doi:10.1111/vop.12065
Zhang C, Gehlbach P, Gongora C, Cano M, Fariss R, Hose S, Nath A, Green WR, Goldberg MF, Zigler JS, Jr., Sinha D (2005) A potential role for beta- and gamma-crystallins in the vascular remodeling of the eye. Dev Dyn 234(1):36–47. doi:10.1002/dvdy.20494
Zhang Y, Ouyang S, Zhang L, Tang X, Song Z, Liu P (2010) Oxygen-induced changes in mitochondrial DNA and DNA repair enzymes in aging rat lens. Mechanisms Ageing Development 131(11/12):666–673. doi:10.1016/j.mad.2010.09.003
Zhang J, Yan H, Lofgren S, Tian X, Lou MF (2012a) Ultraviolet radiation-induced cataract in mice: the effect of age and the potential biochemical mechanism. Invest Ophthalmol Vis Sci 53(11):7276–7285. doi:10.1167/iovs.12-10482
Zhang P, Xing K, Randazzo J, Blessing K, Lou MF, Kador PF (2012b) Osmotic stress, not aldose reductase activity, directly induces growth factors and MAPK signaling changes during sugar cataract formation. Exp Eye Res 101:36–43. doi:10.1016/j.exer.2012.05.007
Zigler JS, Jr. (1990) Animal models for the study of maturity-onset and hereditary cataract. Exp Eye Res 50(6):651–657
Zigler JS, Jr., Rao PV (1991) Enzyme/crystallins and extremely high pyridine nucleotide levels in the eye lens. FASEB J 5(2):223–225
Zigman S, Datiles M, Torczynski E (1979) Sunlight and human cataracts. Invest Ophthalmol Vis Sci 18(5):462–467
Compliance with Ethical Requirements
Judith West-Mays, Scott Bowman and Yizhi Liu declare that they have no conflict of interest.
No human or animal studies were performed by the authors for this article.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
West-Mays, J., Bowman, S. (2016). Animal Models of Cataracts. In: Chan, CC. (eds) Animal Models of Ophthalmic Diseases. Essentials in Ophthalmology. Springer, Cham. https://doi.org/10.1007/978-3-319-19434-9_2
Download citation
DOI: https://doi.org/10.1007/978-3-319-19434-9_2
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-19433-2
Online ISBN: 978-3-319-19434-9
eBook Packages: MedicineMedicine (R0)