1932

Abstract

Cataract, the clinical correlate of opacity or light scattering in the eye lens, is usually caused by the presence of high-molecular-weight (HMW) protein aggregates or disruption of the lens microarchitecture. In general, genes involved in inherited cataracts reflect important processes and pathways in the lens including lens crystallins, connexins, growth factors, membrane proteins, intermediate filament proteins, and chaperones. Usually, mutations causing severe damage to proteins cause congenital cataracts, while milder variants increasing susceptibility to environmental insults are associated with age-related cataracts. These may have different pathogenic mechanisms: Congenital cataracts induce the unfolded protein response and apoptosis. By contrast, denatured crystallins in age-related cataracts are bound by α-crystallin and form light-scattering HMW aggregates. New therapeutic approaches to age-related cataracts use chemical chaperones to solubilize HMW aggregates, while attempts are being made to regenerate lenses using endogenous stem cells to treat congenital cataracts.

Keyword(s): cataractcrystallingeneticslens
Loading

Article metrics loading...

/content/journals/10.1146/annurev-vision-091517-034346
2019-09-15
2024-06-22
Loading full text...

Full text loading...

/deliver/fulltext/vision/5/1/annurev-vision-091517-034346.html?itemId=/content/journals/10.1146/annurev-vision-091517-034346&mimeType=html&fmt=ahah

Literature Cited

  1. Abdelkader H, Alany RG, Pierscionek B 2015. Age-related cataract and drug therapy: opportunities and challenges for topical antioxidant delivery to the lens. J. Pharm. Pharmacol. 67:537–50
    [Google Scholar]
  2. Abe T, Furui S, Sasaki H, Sakamoto Y, Suzuki S et al. 2012. Quantitative evaluation of light scattering intensities of the crystalline lens for radiation related minimal change in interventional radiologists: a cross-sectional pilot study. J. Radiat. Res. 54:315–21
    [Google Scholar]
  3. Alapure BV, Stull JK, Firtina Z, Duncan MK 2012. The unfolded protein response is activated in connexin 50 mutant mouse lenses. Exp. Eye Res. 102:28–37
    [Google Scholar]
  4. Aldahmesh MA, Khan AO, Mohamed JY, Alghamdi MH, Alkuraya FS 2012. Identification of a truncation mutation of the acylglycerol kinase (AGK) gene in a novel autosomal recessive cataract locus. Hum. Mutat. 33:960–62
    [Google Scholar]
  5. Aldahmesh MA, Khan AO, Mohamed JY, Alkuraya FS 2011. Novel recessive BFSP2 and PITX3 mutations: insights into mutational mechanisms from consanguineous populations. Genet. Med. 13:978–81
    [Google Scholar]
  6. Aldahmesh MA, Khan AO, Mohamed JY, Hijazi H, Al-Owain M et al. 2012. Genomic analysis of pediatric cataract in Saudi Arabia reveals novel candidate disease genes. Genet. Med. 14:955–62
    [Google Scholar]
  7. Amaya L, Taylor D, Russell-Eggitt I, Nischal KK, Lengyel D 2003. The morphology and natural history of childhood cataracts. Surv. Ophthalmol. 48:125–44
    [Google Scholar]
  8. Andley UP, Goldman JW. 2015. Autophagy and UPR in alpha-crystallin mutant knock-in mouse models of hereditary cataracts. Biochim. Biophys. Acta 1860:234–39
    [Google Scholar]
  9. Ansar M, Chung HL, Taylor RL, Nazir A, Imtiaz S et al. 2018. Bi-allelic loss-of-function variants in DNMBP cause infantile cataracts. Am. J. Hum. Genet. 103:568–78
    [Google Scholar]
  10. Beaumont C, Leneuve P, Devaux I, Scoazec JY, Berthier M et al. 1995. Mutation in the iron responsive element of the L ferritin mRNA in a family with dominant hyperferritinaemia and cataract. Nat. Genet. 11:444–46
    [Google Scholar]
  11. Benedek GB. 1971. Theory of transparency of the eye. Appl. Opt. 10:459–73
    [Google Scholar]
  12. Benito A, Hervella L, Tabernero J, Pennos A, Ginis H et al. 2016. Environmental and genetic factors explain differences in intraocular scattering. Invest. Ophthalmol. Vis. Sci. 57:163–68
    [Google Scholar]
  13. Berry V, Francis P, Reddy MA, Collyer D, Vithana E et al. 2001. Alpha-B crystallin gene (CRYAB) mutation causes dominant congenital posterior polar cataract in humans. Am. J. Hum. Genet. 69:1141–45
    [Google Scholar]
  14. Berthoud VM, Minogue PJ, Guo J, Williamson EK, Xu X et al. 2003. Loss of function and impaired degradation of a cataract-associated mutant connexin50. Eur. J. Cell Biol. 82:209–21
    [Google Scholar]
  15. Bhagyalaxmi SG, Padma T, Reddy GB, Reddy KR 2010. Association of G>A transition in exon-1 of alpha crystallin gene in age-related cataracts. Oman J. Ophthalmol. 3:7–12
    [Google Scholar]
  16. Bhagyalaxmi SG, Srinivas P, Barton KA, Kumar KR, Vidyavathi M et al. 2009. A novel mutation (F71L) in αA-crystallin with defective chaperone-like function associated with age-related cataract. Biochim. Biophys. Acta 1792:974–81
    [Google Scholar]
  17. Brady JP, Garland D, Duglas-Tabor Y, Robison WG Jr., Groome A, Wawrousek EF. 1997. Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin. PNAS 94:884–89
    [Google Scholar]
  18. Brady JP, Garland DL, Green DE, Tamm ER, Giblin FJ, Wawrousek EF 2001. αB-crystallin in lens development and muscle integrity: a gene knockout approach. Invest. Ophthalmol. Vis. Sci. 42:2924–34
    [Google Scholar]
  19. Brennan LA, Kantorow WL, Chauss D, McGreal R, He S et al. 2012. Spatial expression patterns of autophagy genes in the eye lens and induction of autophagy in lens cells. Mol. Vis. 18:1773–86
    [Google Scholar]
  20. Brennan LA, McGreal-Estrada R, Logan CM, Cvekl A, Menko AS, Kantorow M 2018. BNIP3L/NIX is required for elimination of mitochondria, endoplasmic reticulum and Golgi apparatus during eye lens organelle-free zone formation. Exp. Eye Res. 174:173–84
    [Google Scholar]
  21. Brown NA, Hill AR. 1987. Cataract: the relation between myopia and cataract morphology. Br. J. Ophthalmol. 71:405–14
    [Google Scholar]
  22. Burdon KP, McKay JD, Sale MM, Russell-Eggitt IM, Mackey DA et al. 2003. Mutations in a novel gene, NHS, cause the pleiotropic effects of Nance-Horan syndrome, including severe congenital cataract, dental anomalies, and mental retardation. Am. J. Hum. Genet. 73:1120–30
    [Google Scholar]
  23. Castorino JJ, Gallagher-Colombo SM, Levin AV, Fitzgerald PG, Polishook J et al. 2011. Juvenile cataract-associated mutation of solute carrier SLC16A12 impairs trafficking of the protein to the plasma membrane. Invest. Ophthalmol. Vis. Sci. 52:6774–84
    [Google Scholar]
  24. Chang JR, Koo E, Agron E, Hallak J, Clemons T et al. 2011. Risk factors associated with incident cataracts and cataract surgery in the Age-Related Eye Disease Study (AREDS): AREDS report number 32. Ophthalmology 118:2113–19
    [Google Scholar]
  25. Chen J, Ma Z, Jiao X, Fariss R, Kantorow WL et al. 2011. Mutations in FYCO1 cause autosomal-recessive congenital cataracts. Am. J. Hum. Genet. 88:827–38
    [Google Scholar]
  26. Chen J, Wang Q, Cabrera PE, Zhong Z, Sun W et al. 2017. Molecular genetic analysis of Pakistani families with autosomal recessive congenital cataracts by homozygosity screening. Invest. Ophthalmol. Vis. Sci. 58:2207–17
    [Google Scholar]
  27. Chen JH, Huang C, Zhang B, Yin S, Liang J et al. 2016. Mutations of RagA GTPase in mTORC1 pathway are associated with autosomal dominant cataracts. PLOS Genet 12:e1006090
    [Google Scholar]
  28. Chen P, Dai Y, Wu X, Wang Y, Sun S et al. 2014. Mutations in the ABCA3 gene are associated with cataract-microcornea syndrome. Invest. Ophthalmol. Vis. Sci. 55:8031–43
    [Google Scholar]
  29. Cohen D, Bar-Yosef U, Levy J, Gradstein L, Belfair N et al. 2007. Homozygous CRYBB1 deletion mutation underlies autosomal recessive congenital cataract. Invest. Ophthalmol. Vis. Sci. 48:2208–13
    [Google Scholar]
  30. Congdon NG, Friedman DS, Lietman T 2003. Important causes of visual impairment in the world today. J. Am. Med. Assoc. 290:2057–60
    [Google Scholar]
  31. Conley YP, Erturk D, Keverline A, Mah TS, Keravala A et al. 2000. A juvenile-onset, progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein–2. Am. J. Hum. Genet. 66:1426–31
    [Google Scholar]
  32. Costello MJ, Brennan LA, Basu S, Chauss D, Mohamed A et al. 2013. Autophagy and mitophagy participate in ocular lens organelle degradation. Exp. Eye Res. 116:141–50
    [Google Scholar]
  33. Datiles MB III, Ansari RR, Suh KI, Vitale S, Reed GF et al. 2008. Clinical detection of precataractous lens protein changes using dynamic light scattering. Arch. Ophthalmol. 126:1687–93
    [Google Scholar]
  34. Dawes LJ, Shelley EJ, McAvoy JW, Lovicu FJ 2018. A role for Hippo/YAP-signaling in FGF-induced lens epithelial cell proliferation and fibre differentiation. Exp. Eye Res. 169:122–33
    [Google Scholar]
  35. Delaye M, Tardieu A. 1983. Short-range order of crystallin proteins accounts for eye lens transparency. Nature 302:415–17
    [Google Scholar]
  36. Eiberg H, Marner E, Rosenberg T, Mohr J 1988. Marner's cataract (CAM) assigned to chromosome 16: linkage to haptoglobin. Clin. Genet. 34:272–75
    [Google Scholar]
  37. Firtina Z, Danysh BP, Bai X, Gould DB, Kobayashi T, Duncan MK 2009. Abnormal expression of collagen IV in lens activates unfolded protein response resulting in cataract. J. Biol. Chem. 284:35872–84
    [Google Scholar]
  38. Forshew T, Johnson CA, Khaliq S, Pasha S, Willis C et al. 2005. Locus heterogeneity in autosomal recessive congenital cataracts: linkage to 9q and germline HSF4 mutations. Hum. Genet. 117:452–59
    [Google Scholar]
  39. Foster PJ, Wong TY, Machin D, Johnson GJ, Seah SK 2003. Risk factors for nuclear, cortical and posterior subcapsular cataracts in the Chinese population of Singapore: the Tanjong Pagar Survey. Br. J. Ophthalmol. 87:1112–20
    [Google Scholar]
  40. Framingham Offspring Eye Study Group 1994. Familial aggregation of lens opacities: the Framingham Eye Study and the Framingham Offspring Eye Study. Am. J. Epidemiol. 140:555–64
    [Google Scholar]
  41. Francis P, Chung JJ, Yasui M, Berry V, Moore A et al. 2000. Functional impairment of lens aquaporin in two families with dominantly inherited cataracts. Hum. Mol. Genet. 9:2329–34
    [Google Scholar]
  42. Francois J. 1982. Genetics of cataract. Ophthalmologica 184:61–71
    [Google Scholar]
  43. Ganea E, Harding JJ. 2006. Glutathione-related enzymes and the eye. Curr. Eye Res. 31:1–11
    [Google Scholar]
  44. Gao J, Minogue PJ, Beyer EC, Mathias RT, Berthoud VM 2018. Disruption of the lens circulation causes calcium accumulation and precipitates in connexin mutant mice. Am. J. Physiol. Cell Physiol. 314:C492–503
    [Google Scholar]
  45. Gilbert C, Foster A. 2001. Childhood blindness in the context of VISION 2020—the right to sight. Bull. World Health Organ. 79:227–32
    [Google Scholar]
  46. Girelli D, Corrocher R, Bisceglia L, Olivieri O, De Franceschi L et al. 1995. Molecular basis for the recently described hereditary hyperferritinemia-cataract syndrome: a mutation in the iron-responsive element of ferritin L-subunit gene (the “Verona mutation”). Blood 86:4050–53
    [Google Scholar]
  47. Glaser T, Jepeal L, Edwards JG, Young SR, Favor J, Maas RL 1994. PAX6 gene dosage effect in a family with congenital cataracts, aniridia, anophthalmia and central nervous system defects. Nat. Genet. 7:463–71
    [Google Scholar]
  48. Gong X, Cheng C, Xia CH 2007. Connexins in lens development and cataractogenesis. J. Membr. Biol. 218:9–12
    [Google Scholar]
  49. Gorman AM, Healy SJ, Jager R, Samali A 2012. Stress management at the ER: regulators of ER stress-induced apoptosis. Pharmacol. Ther. 134:306–16
    [Google Scholar]
  50. Gupta S, Cuffe L, Szegezdi E, Logue SE, Neary C et al. 2010. Mechanisms of ER stress-mediated mitochondrial membrane permeabilization. Int. J. Cell Biol. 2010:170215
    [Google Scholar]
  51. Gupta S, Read DE, Deepti A, Cawley K, Gupta A et al. 2012. Perk-dependent repression of miR-106b-25 cluster is required for ER stress-induced apoptosis. Cell Death Dis 3:e333
    [Google Scholar]
  52. Haargaard B, Wohlfahrt J, Fledelius HC, Rosenberg T, Melbye M 2004. Incidence and cumulative risk of childhood cataract in a cohort of 2.6 million Danish children. Invest. Ophthalmol. Vis. Sci. 45:1316–20
    [Google Scholar]
  53. Haargaard B, Wohlfahrt J, Rosenberg T, Fledelius HC, Melbye M 2005. Risk factors for idiopathic congenital/infantile cataract. Invest. Ophthalmol. Vis. Sci. 46:3067–73
    [Google Scholar]
  54. Hammond CJ, Duncan DD, Snieder H, de Lange M, West SK et al. 2001. The heritability of age-related cortical cataract: the Twin Eye Study. Invest. Ophthalmol. Vis. Sci. 42:601–5
    [Google Scholar]
  55. Hammond CJ, Snieder H, Spector TD, Gilbert CE 2000. Genetic and environmental factors in age-related nuclear cataracts in monozygotic and dizygotic twins. New Engl. J. Med. 342:1786–90
    [Google Scholar]
  56. Hansen L, Comyn S, Mang Y, Lind-Thomsen A, Myhre L et al. 2014. The myosin chaperone UNC45B is involved in lens development and autosomal dominant juvenile cataract. Eur. J. Hum. Genet. 22:1290–97
    [Google Scholar]
  57. Haslbeck M, Peschek J, Buchner J, Weinkauf S 2015. Structure and function of α-crystallins: traversing from in vitro to in vivo. Biochim. Biophys. Acta 1860:149–66
    [Google Scholar]
  58. Heiba IM, Elston RC, Klein BE, Klein R 1993. Genetic etiology of nuclear cataract: evidence for a major gene. Am. J. Med. Genet. 47:1208–14
    [Google Scholar]
  59. Heiba IM, Elston RC, Klein BE, Klein R 1995. Evidence for a major gene for cortical cataract. Invest. Ophthalmol. Vis. Sci. 36:227–35
    [Google Scholar]
  60. Hejtmancik JF, Kaiser-Kupfer MI, Piatigorsky J 2001. Molecular biology and inherited disorders of the eye lens. The Metabolic and Molecular Bases of Inherited Disease CR Scriver, AL Beaudet, D Valle, WS Sly, B Childs et al.6033–62 New York: McGraw Hill
    [Google Scholar]
  61. Hejtmancik JF, Kantorow M. 2004. Molecular genetics of age-related cataract. Exp. Eye Res. 79:3–9
    [Google Scholar]
  62. Hejtmancik JF, Smaoui N. 2003. Molecular genetics of cataract. Genetics in Ophthalmology B Wissinger, S Kohl, U Langenbeck 67–82 Basel, Switz.: S. Karger
    [Google Scholar]
  63. Hennis A, Wu SY, Nemesure B, Leske MC 2004. Risk factors for incident cortical and posterior subcapsular lens opacities in the Barbados Eye Studies. Arch. Ophthalmol. 122:525–30
    [Google Scholar]
  64. Horwitz J. 2003. Alpha-crystallin. Exp. Eye Res. 76:145–53
    [Google Scholar]
  65. Ikesugi K, Yamamoto R, Mulhern ML, Shinohara T 2006. Role of the unfolded protein response (UPR) in cataract formation. Exp. Eye Res. 83:508–16
    [Google Scholar]
  66. Italian-American Cataract Study Group 1991. Risk factors for age-related cortical, nuclear, and posterior subcapsular cataracts. Am. J. Epidemiol. 133:541–53
    [Google Scholar]
  67. Iyengar SK, Klein BE, Klein R, Jun G, Schick JH et al. 2004. Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study. PNAS 101:14485–90
    [Google Scholar]
  68. Jaenicke R, Slingsby C. 2001. Lens crystallins and their microbial homologs: structure, stability, and function. Crit. Rev. Biochem. Mol. Biol. 36:435–99
    [Google Scholar]
  69. Jakobs PM, Hess JF, FitzGerald PG, Kramer P, Weleber RG, Litt M 2000. Autosomal-dominant congenital cataract associated with a deletion mutation in the human beaded filament protein gene BFSP2. Am. J. Hum. Genet 66:1432–36
    [Google Scholar]
  70. Jamieson RV, Farrar N, Stewart K, Perveen R, Mihelec M et al. 2007. Characterization of a familial t(16;22) balanced translocation associated with congenital cataract leads to identification of a novel gene, TMEM114, expressed in the lens and disrupted by the translocation. Hum. Mutat. 28:968–77
    [Google Scholar]
  71. Jiao X, Khan SY, Irum B, Khan AO, Wang Q et al. 2015. Missense mutations in CRYAB are liable for recessive congenital cataracts. PLOS ONE 10:e0137973
    [Google Scholar]
  72. Jun G, Guo H, Klein BE, Klein R, Wang JJ et al. 2009. EPHA2 is associated with age-related cortical cataract in mice and humans. PLOS Genet 5:e1000584
    [Google Scholar]
  73. Kamachi Y, Uchikawa M, Tanouchi A, Sekido R, Kondoh H 2001. Pax6 and SOX2 form a co-DNA-binding partner complex that regulates initiation of lens development. Genes Dev 15:1272–86
    [Google Scholar]
  74. Kang H, Yang Z, Zhou R 2018. Lanosterol disrupts aggregation of human γD-crystallin by binding to the hydrophobic dimerization interface. J. Am. Chem. Soc. 140:8479–86
    [Google Scholar]
  75. Kanthan GL, Mitchell P, Burlutsky G, Wang JJ 2010. Alcohol consumption and the long-term incidence of cataract and cataract surgery: the Blue Mountains Eye Study. Am. J. Ophthalmol. 150:434–40.e1
    [Google Scholar]
  76. Kantorow M, Hawse JR, Cowell TL, Benhamed S, Pizarro GO et al. 2004. Methionine sulfoxide reductase A is important for lens cell viability and resistance to oxidative stress. PNAS 101:9654–59
    [Google Scholar]
  77. Kaul H, Riazuddin SA, Shahid M, Kousar S, Butt NH et al. 2010. Autosomal recessive congenital cataract linked to EPHA2 in a consanguineous Pakistani family. Mol. Vis. 16:511–17
    [Google Scholar]
  78. 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. 144:949–52.e2
    [Google Scholar]
  79. Khan AO, Aldahmesh MA, Mohamed JY, Alkuraya FS 2012. Clinical and molecular analysis of children with central pulverulent cataract from the Arabian Peninsula. Br. J. Ophthalmol. 96:650–5
    [Google Scholar]
  80. Kingsley CN, Brubaker WD, Markovic S, Diehl A, Brindley AJ et al. 2013. Preferential and specific binding of human αB-crystallin to a cataract-related variant of γS-crystallin. Structure 21:2221–27
    [Google Scholar]
  81. Kinoshita JH. 1965. Cataracts in galactosemia: the Jonas Friedenwald Memorial Lecture. Invest. Ophthalmol. 4:786–99
    [Google Scholar]
  82. Klein BE, Klein R, Lee KE, Moore EL, Danforth L 2001. Risk of incident age-related eye diseases in people with an affected sibling: the Beaver Dam Eye Study. Am. J. Epidemiol. 154:207–11
    [Google Scholar]
  83. Kloeckener-Gruissem B, Vandekerckhove K, Nurnberg G, Neidhardt J, Zeitz C et al. 2008. Mutation of solute carrier SLC16A12 associates with a syndrome combining juvenile cataract with microcornea and renal glucosuria. Am. J. Hum. Genet. 82:772–79
    [Google Scholar]
  84. Kmoch S, Brynda J, Asfaw B, Bezouska K, Novak P et al. 2000. Link between a novel human γD-crystallin allele and a unique cataract phenotype explained by protein crystallography. Hum. Mol. Genet. 9:1779–86
    [Google Scholar]
  85. Kumar M, Kaur P, Khokhar S, Dada R 2013. Molecular and structural analysis of genetic variations in congenital cataract. Mol. Vis. 19:2436–50
    [Google Scholar]
  86. Kupfer C. 1984. The Bowman Lecture: the conquest of cataract; a global challenge. Surv. Ophthalmol. 30:271
    [Google Scholar]
  87. Lachke SA, Alkuraya FS, Kneeland SC, Ohn T, Aboukhalil A et al. 2011. Mutations in the RNA granule component TDRD7 cause cataract and glaucoma. Science 331:1571–76
    [Google Scholar]
  88. Lai E, Teodoro T, Volchuk A 2007. Endoplasmic reticulum stress: signaling the unfolded protein response. Physiology 22:193–201
    [Google Scholar]
  89. 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. PNAS 92:2780–84
    [Google Scholar]
  90. Lee SC, Wang Y, Ko GT, Ma RC, Critchley JA et al. 2001. Risk factors for cataract in Chinese patients with type 2 diabetes: evidence for the influence of the aldose reductase gene. Clin. Genet. 59:356–59
    [Google Scholar]
  91. Leske MC, Chylack LT Jr., He Q, Wu SY, Schoenfeld E et al. 1998. Risk factors for nuclear opalescence in a longitudinal study. Am. J. Epidemiol. 147:36–41
    [Google Scholar]
  92. Leske MC, Chylack LT Jr., Wu SY 1991. The Lens Opacities Case-Control Study. Risk factors for cataract. Arch. Ophthalmol. 109:244–51
    [Google Scholar]
  93. Li D, Wang S, Ye H, Tang Y, Qiu X et al. 2016. Distribution of gene mutations in sporadic congenital cataract in a Han Chinese population. Mol. Vis. 22:589–98
    [Google Scholar]
  94. Li L, Fan DB, Zhao YT, Li Y, Kong DQ et al. 2017. Two novel mutations identified in ADCC families impair crystallin protein distribution and induce apoptosis in human lens epithelial cells. Sci. Rep. 7:17848
    [Google Scholar]
  95. Liao J, Su X, Chen P, Wang X, Xu L et al. 2014. Meta-analysis of genome-wide association studies in multiethnic Asians identifies two loci for age-related nuclear cataract. Hum. Mol. Genet. 23:6119–28
    [Google Scholar]
  96. Lin H, Lin D, Liu Z, Long E, Wu X et al. 2016a. A novel congenital cataract category system based on lens opacity locations and relevant anterior segment characteristics. Invest. Ophthalmol. Vis. Sci. 57:6389–95
    [Google Scholar]
  97. Lin H, Ouyang H, Zhu J, Huang S, Liu Z et al. 2016b. Lens regeneration using endogenous stem cells with gain of visual function. Nature 531:323–28
    [Google Scholar]
  98. Linetsky M, Shipova E, Cheng R, Ortwerth BJ 2008. Glycation by ascorbic acid oxidation products leads to the aggregation of lens proteins. Biochim. Biophys. Acta 1782:22–34
    [Google Scholar]
  99. Lu ZQ, Sun WH, Yan J, Jiang TX, Zhai SN, Li Y 2012. Cigarette smoking, body mass index associated with the risks of age-related cataract in male patients in northeast China. Int. J. Ophthalmol. 5:317–22
    [Google Scholar]
  100. Ma AS, Grigg JR, Ho G, Prokudin I, Farnsworth E et al. 2016a. Sporadic and familial congenital cataracts: mutational spectrum and new diagnoses using next-generation sequencing. Hum. Mutat. 37:371–84
    [Google Scholar]
  101. Ma X, Jiao X, Ma Z, Hejtmancik JF 2016b. Polymorphism rs7278468 is associated with age-related cataract through decreasing transcriptional activity of the CRYAA promoter. Sci. Rep. 6:23206
    [Google Scholar]
  102. Ma X, Ma Z, Jiao X, Hejtmancik JF 2017. Functional non-coding polymorphism in an EPHA2 promoter PAX2 binding site modifies expression and alters the MAPK and AKT pathways. Sci. Rep. 7:9992
    [Google Scholar]
  103. Ma Z, Piszczek G, Wingfield PT, Sergeev YV, Hejtmancik JF 2009. The G18V CRYGS mutation associated with human cataracts increases γS-crystallin sensitivity to thermal and chemical stress. Biochemistry 48:7334–41
    [Google Scholar]
  104. Ma Z, Yao W, Chan CC, Kannabiran C, Wawrousek E, Hejtmancik JF 2016c. Human βA3/A1-crystallin splicing mutation causes cataracts by activating the unfolded protein response and inducing apoptosis in differentiating lens fiber cells. Biochim. Biophys. Acta 1862:1214–27
    [Google Scholar]
  105. Ma Z, Yao W, Theendakara V, Chan CC, Wawrousek E, Hejtmancik JF 2011. Overexpression of human γC-crystallin 5 bp duplication disrupts lens morphology in transgenic mice. Invest. Ophthalmol. Vis. Sci. 52:5269–375
    [Google Scholar]
  106. Machan CM, Hrynchak PK, Irving EL 2012. Age-related cataract is associated with type 2 diabetes and statin use. Optom. Vis. Sci. 89:1165–71
    [Google Scholar]
  107. Makley LN, McMenimen KA, DeVree BT, Goldman JW, McGlasson BN et al. 2015. Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. Science 350:674–77
    [Google Scholar]
  108. McCarty CA, Taylor HR. 2001. The genetics of cataract. Invest. Ophthalmol. Vis. Sci. 42:1677–78
    [Google Scholar]
  109. 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. 279:3413–19
    [Google Scholar]
  110. Merin S. 1991. Inherited cataracts. Inherited Eye Diseases S Merin 86–120 New York: Marcel Dekker
    [Google Scholar]
  111. Merin S, Crawford JS. 1971. The etiology of congenital cataracts. A survey of 386 cases. Can. J. Ophthalmol. 6:178–82
    [Google Scholar]
  112. Minogue PJ, Liu X, Ebihara L, Beyer EC, Berthoud VM 2005. An aberrant sequence in a connexin46 mutant underlies congenital cataracts. J. Biol. Chem. 280:40788–95
    [Google Scholar]
  113. Moreau KL, King JA. 2012a. Cataract-causing defect of a mutant γ-crystallin proceeds through an aggregation pathway which bypasses recognition by the α-crystallin chaperone. PLOS ONE 7:e37256
    [Google Scholar]
  114. Moreau KL, King JA. 2012b. Protein misfolding and aggregation in cataract disease and prospects for prevention. Trends Mol. Med. 18:273–82
    [Google Scholar]
  115. Mulhern ML, Madson CJ, Danford A, Ikesugi K, Kador PF, Shinohara T 2006. The unfolded protein response in lens epithelial cells from galactosemic rat lenses. Invest. Ophthalmol. Vis. Sci. 47:3951–59
    [Google Scholar]
  116. Okano Y, Asada M, Fujimoto A, Ohtake A, Murayama K et al. 2001. A genetic factor for age-related cataract: identification and characterization of a novel galactokinase variant, “Osaka,” in Asians. Am. J. Hum. Genet. 68:1036–42
    [Google Scholar]
  117. Ottonello S, Foroni C, Carta A, Petrucco S, Maraini G 2000. Oxidative stress and age-related cataract. Ophthalmologica 214:78–85
    [Google Scholar]
  118. Pal JD, Liu X, Mackay D, Shiels A, Berthoud VM et al. 2000. Connexin46 mutations linked to congenital cataract show loss of gap junction channel function. Am. J. Physiol. Cell Physiol. 279:C596–602
    [Google Scholar]
  119. Palsamy P, Bidasee KR, Shinohara T 2014. Selenite cataracts: activation of endoplasmic reticulum stress and loss of Nrf2/Keap1-dependent stress protection. Biochim. Biophys. Acta 1842:1794–805
    [Google Scholar]
  120. Pande A, Pande J, Asherie N, Lomakin A, Ogun O et al. 2000. Molecular basis of a progressive juvenile-onset hereditary cataract. PNAS 97:1993–98
    [Google Scholar]
  121. Pande A, Pande J, Asherie N, Lomakin A, Ogun O et al. 2001. Crystal cataracts: human genetic cataract caused by protein crystallization. PNAS 98:6116–20
    [Google Scholar]
  122. Park S, Choi NK. 2017. Serum 25-hydroxyvitamin D and age-related cataract. Ophthalmic Epidemiol 24:281–86
    [Google Scholar]
  123. Pascolini D, Mariotti SP. 2012. Global estimates of visual impairment: 2010. Br. J. Ophthalmol. 96:614–18
    [Google Scholar]
  124. Pras E, Frydman M, Levy-Nissenbaum E, Bakhan T, Raz J et al. 2000. A nonsense mutation (W9X) in CRYAA causes autosomal recessive cataract in an inbred Jewish Persian family. Invest. Ophthalmol. Vis. Sci. 41:3511–15
    [Google Scholar]
  125. Pras E, Levy-Nissenbaum E, Bakhan T, Lahat H, Assia E et al. 2002. A missense mutation in the LIM2 gene is associated with autosomal recessive presenile cataract in an inbred Iraqi Jewish family. Am. J. Hum. Genet. 70:1363–67
    [Google Scholar]
  126. Rajaraman K, Raman B, Ramakrishna T, Rao CM 1998. The chaperone-like α-crystallin forms a complex only with the aggregation-prone molten globule state of α-lactalbumin. Biochem. Biophys. Res. Commun. 249:917–21
    [Google Scholar]
  127. Ramachandran RD, Perumalsamy V, Hejtmancik JF 2007. Autosomal recessive juvenile onset cataract associated with mutation in BFSP1. Hum. Genet 121:475–82
    [Google Scholar]
  128. Rao GN, Khanna R, Payal A 2011. The global burden of cataract. Curr. Opin. Ophthalmol. 22:4–9
    [Google Scholar]
  129. Rao PV, Huang QL, Horwitz J, Zigler JS Jr 1995. Evidence that α-crystallin prevents non-specific protein aggregation in the intact eye lens. Biochim. Biophys. Acta 1245:439–47
    [Google Scholar]
  130. Rasheva VI, Domingos PM. 2009. Cellular responses to endoplasmic reticulum stress and apoptosis. Apoptosis 14:996–1007
    [Google Scholar]
  131. Ravindran RD, Vashist P, Gupta SK, Young IS, Maraini G et al. 2011. Inverse association of vitamin C with cataract in older people in India. Ophthalmology 118:1958–65.e2
    [Google Scholar]
  132. Ren Z, Li A, Shastry BS, Padma T, Ayyagari R et al. 2000. A 5-base insertion in the γC-crystallin gene is associated with autosomal dominant variable zonular pulverulent cataract. Hum. Genet. 106:531–37
    [Google Scholar]
  133. Riazuddin SA, Yasmeen A, Yao W, Sergeev YV, Zhang Q et al. 2005. Mutations in βB3-crystallin associated with autosomal recessive cataract in two Pakistani families. Invest. Ophthalmol. Vis. Sci. 46:2100–6
    [Google Scholar]
  134. Safieh LA, Khan AO, Alkuraya FS 2009. Identification of a novel CRYAB mutation associated with autosomal recessive juvenile cataract in a Saudi family. Mol. Vis. 15:980–84
    [Google Scholar]
  135. Sathish HA, Koteiche HA, McHaourab HS 2004. Binding of destabilized βB2-crystallin mutants to α-crystallin: the role of a folding intermediate. J. Biol. Chem. 279:16425–32
    [Google Scholar]
  136. Schroder M, Kaufman RJ. 2005. The mammalian unfolded protein response. Annu. Rev. Biochem. 74:739–89
    [Google Scholar]
  137. Scriver CR, Beaudet AL, Valle D, Sly WS, Childs B et al., eds. 2005. The Metabolic and Molecular Bases of Inherited Disease New York: McGraw-Hill
    [Google Scholar]
  138. Scott MH, Hejtmancik JF, Wozencraft LA, Reuter LM, Parks MM, Kaiser-Kupfer MI 1994. Autosomal dominant congenital cataract: interocular phenotypic heterogeneity. Ophthalmology 101:866–71
    [Google Scholar]
  139. Shanmugam PM, Barigali A, Kadaskar J, Borgohain S, Mishra DK et al. 2015. Effect of lanosterol on human cataract nucleus. Indian J. Ophthalmol. 63:888–90
    [Google Scholar]
  140. Sharma KK, Santhoshkumar P. 2009. Lens aging: effects of crystallins. Biochim. Biophys. Acta 1790:1095–108
    [Google Scholar]
  141. Shiels A, Bennett TM, Hejtmancik JF 2010. Cat-Map: putting cataract on the map. Mol. Vis. 16:2007–15
    [Google Scholar]
  142. Shiels A, Bennett TM, Knopf HL, Maraini G, Li A et al. 2008. The EPHA2 gene is associated with cataracts linked to chromosome 1p. Mol. Vis. 14:2042–55
    [Google Scholar]
  143. Shiels A, Bennett TM, Knopf HL, Yamada K, Yoshiura K et al. 2007. CHMP4B, a novel gene for autosomal dominant cataracts linked to chromosome 20q. Am. J. Hum. Genet. 81:596–606
    [Google Scholar]
  144. Shiels A, Hejtmancik JF. 2017. Mutations and mechanisms in congenital and age-related cataracts. Exp. Eye Res. 156:95–102
    [Google Scholar]
  145. Skalka HW, Prchal JT. 1980. Presenile cataract formation and decreased activity of galactosemic enzymes. Arch. Ophthalmol. 98:269–73
    [Google Scholar]
  146. Smaoui N, Beltaief O, Benhamed S, M'Rad R, Maazoul F et al. 2004. A homozygous splice mutation in the HSF4 gene is associated with an autosomal recessive congenital cataract. Invest. Ophthalmol. Vis. Sci. 45:2716–21
    [Google Scholar]
  147. Somasundaram T, Bhat SP. 2004. Developmentally dictated expression of heat shock factors: exclusive expression of HSF4 in the postnatal lens and its specific interaction with αB-crystallin heat shock promoter. J. Biol. Chem. 279:44497–503
    [Google Scholar]
  148. Sovolyova N, Healy S, Samali A, Logue SE 2014. Stressed to death—mechanisms of ER stress-induced cell death. Biol. Chem. 395:1–13
    [Google Scholar]
  149. Staubli A, Capatina N, Fuhrer Y, Munier FL, Labs S et al. 2017. Abnormal creatine transport of mutations in monocarboxylate transporter 12 (MCT12) found in patients with age-related cataract can be partially rescued by exogenous chaperone CD147. Hum. Mol. Genet. 26:4203–14
    [Google Scholar]
  150. Stevens RE, Datiles MB, Srivastava SK, Ansari NH, Maumenee AE, Stark WJ 1989. Idiopathic presenile cataract formation and galactosaemia. Br. J. Ophthalmol. 73:48–51
    [Google Scholar]
  151. Stoll C, Alembik Y, Dott B, Roth MP 1992. Epidemiology of congenital eye malformations in 131,760 consecutive births. Ophthalmic Paediatr. Genet. 13:179–86
    [Google Scholar]
  152. Sun H, Ma Z, Li Y, Liu B, Li Z et al. 2005. Gamma-S crystallin gene (CRYGS) mutation causes dominant progressive cortical cataract in humans. J. Med. Genet. 42:706–10
    [Google Scholar]
  153. Sun L, Xi B, Yu L, Gao XC, Shi DJ et al. 2010. Association of glutathione S-transferases polymorphisms (GSTM1 and GSTT1) with senile cataract: a meta-analysis. Invest. Ophthalmol. Vis. Sci. 51:6381–86
    [Google Scholar]
  154. Sundaresan P, Ravindran RD, Vashist P, Shanker A, Nitsch D et al. 2012. EPHA2 polymorphisms and age-related cataract in India. PLOS ONE 7:e33001
    [Google Scholar]
  155. Szegezdi E, Herbert KR, Kavanagh ET, Samali A, Gorman AM 2008. Nerve growth factor blocks thapsigargin-induced apoptosis at the level of the mitochondrion via regulation of Bim. J. Cell Mol. Med. 12:2482–96
    [Google Scholar]
  156. Tan W, Hou S, Jiang Z, Hu Z, Yang P, Ye J 2011. Association of EPHA2 polymorphisms and age-related cortical cataract in a Han Chinese population. Mol. Vis. 17:1553–58
    [Google Scholar]
  157. Taylor HR. 2000. Cataract: How much surgery do we have to do?. Br. J. Ophthalmol. 84:1–2
    [Google Scholar]
  158. Toh T, Morton J, Coxon J, Elder MJ 2007. Medical treatment of cataract. Clin. Exp. Ophthalmol. 35:664–71
    [Google Scholar]
  159. Vicart P, Caron A, Guicheney P, Li Z, Prevost MC et al. 1998. A missense mutation in the αB-crystallin chaperone gene causes a desmin-related myopathy. Nat. Genet. 20:92–95
    [Google Scholar]
  160. Wang K, Cheng C, Li L, Liu H, Huang Q et al. 2007. γD-crystallin associated protein aggregation and lens fiber cell denucleation. Invest. Ophthalmol. Vis. Sci. 48:3719–28
    [Google Scholar]
  161. West SK, Valmadrid CT. 1995. Epidemiology of risk factors for age-related cataract. Surv. Ophthalmol. 39:323–34
    [Google Scholar]
  162. Williams PT. 2012. Walking and running are associated with similar reductions in cataract risk. Med. Sci. Sports Exerc. 45:1089–96
    [Google Scholar]
  163. Wride MA. 2011. Lens fibre cell differentiation and organelle loss: Many paths lead to clarity. Philos. Trans. R. Soc. B 366:1219–33
    [Google Scholar]
  164. Xi YB, Chen XJ, Zhao WJ, Yan YB 2015. Congenital cataract-causing mutation G129C in γC-crystallin promotes the accumulation of two distinct unfolding intermediates that form highly toxic aggregates. J. Mol. Biol. 427:2765–81
    [Google Scholar]
  165. Yang J, Zhou S, Gu J, Wang Y, Guo M, Liu Y 2015. Differences in unfolded protein response pathway activation in the lenses of three types of cataracts. PLOS ONE 10:e0130705
    [Google Scholar]
  166. Ye J, He J, Wang C, Wu H, Shi X et al. 2012. Smoking and risk of age-related cataract: a meta-analysis. Invest. Ophthalmol. Vis. Sci. 53:3885–95
    [Google Scholar]
  167. Yonova-Doing E, Forkin ZA, Hysi PG, Williams KM, Spector TD et al. 2016. Genetic and dietary factors influencing the progression of nuclear cataract. Ophthalmology 123:1237–44
    [Google Scholar]
  168. Yu LC, Twu YC, Chou ML, Reid ME, Gray AR et al. 2003. The molecular genetics of the human I locus and molecular background explain the partial association of the adult i phenotype with congenital cataracts. Blood 101:2081–88
    [Google Scholar]
  169. Zhai Y, Li J, Yu W, Zhu S, Yu Y et al. 2017. Targeted exome sequencing of congenital cataracts related genes: broadening the mutation spectrum and genotype-phenotype correlations in 27 Chinese Han families. Sci. Rep. 7:1219
    [Google Scholar]
  170. Zhang T, Hua R, Xiao W, Burdon KP, Bhattacharya SS et al. 2009. Mutations of the EPHA2 receptor tyrosine kinase gene cause autosomal dominant congenital cataract. Hum. Mutat. 30:E603–11
    [Google Scholar]
  171. Zhao L, Chen XJ, Zhu J, Xi YB, Yang X et al. 2015. Lanosterol reverses protein aggregation in cataracts. Nature 523:607–11
    [Google Scholar]
  172. Zhao Z, Fan Q, Zhou P, Ye H, Cai L, Lu Y 2017. Association of αA-crystallin polymorphisms with susceptibility to nuclear age-related cataract in a Han Chinese population. BMC Ophthalmol 17:133
    [Google Scholar]
  173. Zuercher J, Neidhardt J, Magyar I, Labs S, Moore AT et al. 2010. Alterations of the 5′ untranslated leader region of SLC16A12 lead to age-related cataract. Invest. Ophthalmol. Vis. Sci. 51:3354–61
    [Google Scholar]
/content/journals/10.1146/annurev-vision-091517-034346
Loading
/content/journals/10.1146/annurev-vision-091517-034346
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error