Regulates Refractive Error and Myopia Development in Mice and Humans


Gene variants identified by GWAS studies to date explain only a small fraction of myopia cases because myopia represents a complex disorder thought to be controlled by dozens or even hundreds of genes. The majority of genetic variants underlying myopia seems to be of small effect and/or low frequency, which makes them difficult to identify using classical genetic approaches, such as GWAS, alone. Here, we combined gene expression profiling in a monkey model of myopia, human GWAS, and a gene-targeted mouse model of myopia to identify one of the “missing” myopia genes, APLP2. We found that a low-frequency risk allele of APLP2 confers susceptibility to myopia only in children exposed to large amounts of daily reading, thus, providing an experimental example of the long-hypothesized gene-environment interaction between nearwork and genes underlying myopia. Functional analysis of APLP2 using an APLP2 knockout mouse model confirmed functional significance of APLP2 in refractive development and implicated a potential role of synaptic transmission at the level of glycinergic amacrine cells of the retina for the development of myopia. Furthermore, mouse studies revealed that lack of Aplp2 has a dose-dependent suppressive effect on susceptibility to form-deprivation myopia, providing a potential gene-specific target for therapeutic intervention to treat myopia.


Vyšlo v časopise: Regulates Refractive Error and Myopia Development in Mice and Humans. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005432
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1005432

Souhrn

Gene variants identified by GWAS studies to date explain only a small fraction of myopia cases because myopia represents a complex disorder thought to be controlled by dozens or even hundreds of genes. The majority of genetic variants underlying myopia seems to be of small effect and/or low frequency, which makes them difficult to identify using classical genetic approaches, such as GWAS, alone. Here, we combined gene expression profiling in a monkey model of myopia, human GWAS, and a gene-targeted mouse model of myopia to identify one of the “missing” myopia genes, APLP2. We found that a low-frequency risk allele of APLP2 confers susceptibility to myopia only in children exposed to large amounts of daily reading, thus, providing an experimental example of the long-hypothesized gene-environment interaction between nearwork and genes underlying myopia. Functional analysis of APLP2 using an APLP2 knockout mouse model confirmed functional significance of APLP2 in refractive development and implicated a potential role of synaptic transmission at the level of glycinergic amacrine cells of the retina for the development of myopia. Furthermore, mouse studies revealed that lack of Aplp2 has a dose-dependent suppressive effect on susceptibility to form-deprivation myopia, providing a potential gene-specific target for therapeutic intervention to treat myopia.


Zdroje

1. Oyster CW (1999) The human eye: structure and function. Sunderland, MA: Sinauer Associates.

2. Wallman J, Winawer J (2004) Homeostasis of eye growth and the question of myopia. Neuron 43: 447–468. 15312645

3. Pararajasegaram R (1999) VISION 2020-the right to sight: from strategies to action. Am J Ophthalmol 128: 359–360. 10511033

4. Vitale S, Ellwein L, Cotch MF, Ferris FL 3rd, Sperduto R (2008) Prevalence of refractive error in the United States, 1999–2004. Arch Ophthalmol 126: 1111–1119. doi: 10.1001/archopht.126.8.1111 18695106

5. Lin LL, Shih YF, Hsiao CK, Chen CJ (2004) Prevalence of myopia in Taiwanese schoolchildren: 1983 to 2000. Ann Acad Med Singapore 33: 27–33.

6. Lam CS, Goldschmidt E, Edwards MH (2004) Prevalence of myopia in local and international schools in Hong Kong. Optom Vis Sci 81: 317–322. 15181356

7. Pesudovs K, Garamendi E, Elliott DB (2006) A quality of life comparison of people wearing spectacles or contact lenses or having undergone refractive surgery. J Refract Surg 22: 19–27. 16447932

8. Rose K, Harper R, Tromans C, Waterman C, Goldberg D, et al. (2000) Quality of life in myopia. Br J Ophthalmol 84: 1031–1034. 10966960

9. Takashima T, Yokoyama T, Futagami S, Ohno-Matsui K, Tanaka H, et al. (2001) The quality of life in patients with pathologic myopia. Jpn J Ophthalmol 45: 84–92. 11163050

10. Alexander LJ (1994) Primary care of the posterior segment. Connecticut: Appleton & Lange.

11. Saw SM, Gazzard G, Shih-Yen EC, Chua WH (2005) Myopia and associated pathological complications. Ophthalmic Physiol Opt 25: 381–391. 16101943

12. Flitcroft DI (2012) The complex interactions of retinal, optical and environmental factors in myopia aetiology. Prog Retin Eye Res 31: 622–660. doi: 10.1016/j.preteyeres.2012.06.004 22772022

13. Pizzarello L, Abiose A, Ffytche T, Duerksen R, Thulasiraj R, et al. (2004) VISION 2020: The Right to Sight: a global initiative to eliminate avoidable blindness. Arch Ophthalmol 122: 615–620. 15078680

14. Morgan IG (2003) The biological basis of myopic refractive error. Clin Exp Optom 86: 276–288. 14558849

15. Young TL (2009) Molecular genetics of human myopia: an update. Optom Vis Sci 86: E8–E22. doi: 10.1097/OPX.0b013e3181940655 19104467

16. Baird PN, Schache M, Dirani M (2010) The GEnes in Myopia (GEM) study in understanding the aetiology of refractive errors. Prog Retin Eye Res 29: 520–542. doi: 10.1016/j.preteyeres.2010.05.004 20576483

17. Wojciechowski R (2011) Nature and nurture: the complex genetics of myopia and refractive error. Clin Genet 79: 301–320. doi: 10.1111/j.1399-0004.2010.01592.x 21155761

18. Verhoeven VJ, Buitendijk GH, Consortium for Refractive E, Myopia, Rivadeneira F, et al. (2013) Education influences the role of genetics in myopia. Eur J Epidemiol 28: 973–980. doi: 10.1007/s10654-013-9856-1 24142238

19. Dirani M, Chamberlain M, Shekar SN, Islam AF, Garoufalis P, et al. (2006) Heritability of refractive error and ocular biometrics: the Genes in Myopia (GEM) twin study. Invest Ophthalmol Vis Sci 47: 4756–4761. 17065484

20. Lopes MC, Andrew T, Carbonaro F, Spector TD, Hammond CJ (2009) Estimating heritability and shared environmental effects for refractive error in twin and family studies. Invest Ophthalmol Vis Sci 50: 126–131. doi: 10.1167/iovs.08-2385 18757506

21. Peet JA, Cotch MF, Wojciechowski R, Bailey-Wilson JE, Stambolian D (2007) Heritability and familial aggregation of refractive error in the Old Order Amish. Invest Ophthalmol Vis Sci 48: 4002–4006. 17724179

22. Klein AP, Suktitipat B, Duggal P, Lee KE, Klein R, et al. (2009) Heritability analysis of spherical equivalent, axial length, corneal curvature, and anterior chamber depth in the Beaver Dam Eye Study. Arch Ophthalmol 127: 649–655. doi: 10.1001/archophthalmol.2009.61 19433716

23. Chen CY, Scurrah KJ, Stankovich J, Garoufalis P, Dirani M, et al. (2007) Heritability and shared environment estimates for myopia and associated ocular biometric traits: the Genes in Myopia (GEM) family study. Hum Genet 121: 511–520. 17205325

24. Wojciechowski R, Congdon N, Bowie H, Munoz B, Gilbert D, et al. (2005) Heritability of refractive error and familial aggregation of myopia in an elderly American population. Invest Ophthalmol Vis Sci 46: 1588–1592. 15851555

25. Solouki AM, Verhoeven VJ, van Duijn CM, Verkerk AJ, Ikram MK, et al. (2010) A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14. Nat Genet 42: 897–901. doi: 10.1038/ng.663 20835239

26. Hysi PG, Young TL, Mackey DA, Andrew T, Fernandez-Medarde A, et al. (2010) A genome-wide association study for myopia and refractive error identifies a susceptibility locus at 15q25. Nat Genet 42: 902–905. doi: 10.1038/ng.664 20835236

27. Li Z, Qu J, Xu X, Zhou X, Zou H, et al. (2011) A genome-wide association study reveals association between common variants in an intergenic region of 4q25 and high-grade myopia in the Chinese Han population. Hum Mol Genet 20: 2861–2868. doi: 10.1093/hmg/ddr169 21505071

28. Shi Y, Qu J, Zhang D, Zhao P, Zhang Q, et al. (2011) Genetic variants at 13q12.12 are associated with high myopia in the han chinese population. Am J Hum Genet 88: 805–813. doi: 10.1016/j.ajhg.2011.04.022 21640322

29. Li YJ, Goh L, Khor CC, Fan Q, Yu M, et al. (2011) Genome-wide association studies reveal genetic variants in CTNND2 for high myopia in Singapore Chinese. Ophthalmology 118: 368–375. doi: 10.1016/j.ophtha.2010.06.016 21095009

30. Verhoeven VJ, Hysi PG, Wojciechowski R, Fan Q, Guggenheim JA, et al. (2013) Genome-wide meta-analyses of multiancestry cohorts identify multiple new susceptibility loci for refractive error and myopia. Nat Genet 45: 314–318. doi: 10.1038/ng.2554 23396134

31. Farbrother JE, Kirov G, Owen MJ, Pong-Wong R, Haley CS, et al. (2004) Linkage analysis of the genetic loci for high myopia on 18p, 12q, and 17q in 51 U.K. families. Invest Ophthalmol Vis Sci 45: 2879–2885. 15326098

32. Gusev A, Bhatia G, Zaitlen N, Vilhjalmsson BJ, Diogo D, et al. (2013) Quantifying missing heritability at known GWAS loci. PLoS Genet 9: e1003993. doi: 10.1371/journal.pgen.1003993 24385918

33. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747–753. doi: 10.1038/nature08494 19812666

34. Eyre-Walker A (2010) Evolution in health and medicine Sackler colloquium: Genetic architecture of a complex trait and its implications for fitness and genome-wide association studies. Proc Natl Acad Sci U S A 107 Suppl 1: 1752–1756. doi: 10.1073/pnas.0906182107 20133822

35. Park JH, Gail MH, Weinberg CR, Carroll RJ, Chung CC, et al. (2011) Distribution of allele frequencies and effect sizes and their interrelationships for common genetic susceptibility variants. Proc Natl Acad Sci U S A 108: 18026–18031. doi: 10.1073/pnas.1114759108 22003128

36. Lassek M, Weingarten J, Einsfelder U, Brendel P, Muller U, et al. (2013) Amyloid precursor proteins are constituents of the presynaptic active zone. J Neurochem 127: 48–56. doi: 10.1111/jnc.12358 23815291

37. Zhang X, Herrmann U, Weyer SW, Both M, Muller UC, et al. (2013) Hippocampal network oscillations in APP/APLP2-deficient mice. PLoS One 8: e61198. doi: 10.1371/journal.pone.0061198 23585881

38. Korte M, Herrmann U, Zhang X, Draguhn A (2012) The role of APP and APLP for synaptic transmission, plasticity, and network function: lessons from genetic mouse models. Exp Brain Res 217: 435–440. doi: 10.1007/s00221-011-2894-6 22006270

39. Weyer SW, Klevanski M, Delekate A, Voikar V, Aydin D, et al. (2011) APP and APLP2 are essential at PNS and CNS synapses for transmission, spatial learning and LTP. EMBO J 30: 2266–2280. doi: 10.1038/emboj.2011.119 21522131

40. Schrenk-Siemens K, Perez-Alcala S, Richter J, Lacroix E, Rahuel J, et al. (2008) Embryonic stem cell-derived neurons as a cellular system to study gene function: lack of amyloid precursor proteins APP and APLP2 leads to defective synaptic transmission. Stem Cells 26: 2153–2163. doi: 10.1634/stemcells.2008-0010 18535156

41. Herard AS, Besret L, Dubois A, Dauguet J, Delzescaux T, et al. (2006) siRNA targeted against amyloid precursor protein impairs synaptic activity in vivo. Neurobiol Aging 27: 1740–1750. 16337035

42. Yang G, Gong YD, Gong K, Jiang WL, Kwon E, et al. (2005) Reduced synaptic vesicle density and active zone size in mice lacking amyloid precursor protein (APP) and APP-like protein 2. Neurosci Lett 384: 66–71. 15919150

43. Wang P, Yang G, Mosier DR, Chang P, Zaidi T, et al. (2005) Defective neuromuscular synapses in mice lacking amyloid precursor protein (APP) and APP-Like protein 2. J Neurosci 25: 1219–1225. 15689559

44. Leach R, Ko M, Krawetz SA (1999) Assignment of amyloid-precursor-like protein 2 gene (APLP2) to 11q24 by fluorescent in situ hybridization. Cytogenet Cell Genet 87: 215–216. 10702673

45. von Koch CS, Zheng H, Chen H, Trumbauer M, Thinakaran G, et al. (1997) Generation of APLP2 KO mice and early postnatal lethality in APLP2/APP double KO mice. Neurobiol Aging 18: 661–669. 9461064

46. Thinakaran G, Kitt CA, Roskams AJ, Slunt HH, Masliah E, et al. (1995) Distribution of an APP homolog, APLP2, in the mouse olfactory system: a potential role for APLP2 in axogenesis. J Neurosci 15: 6314–6326. 7472397

47. von Koch CS, Lahiri DK, Mammen AL, Copeland NG, Gilbert DJ, et al. (1995) The mouse APLP2 gene. Chromosomal localization and promoter characterization. J Biol Chem 270: 25475–25480. 7592716

48. Sandbrink R, Masters CL, Beyreuther K (1994) Complete nucleotide and deduced amino acid sequence of rat amyloid protein precursor-like protein 2 (APLP2/APPH): two amino acids length difference to human and murine homologues. Biochim Biophys Acta 1219: 167–170. 8086458

49. von der Kammer H, Loffler C, Hanes J, Klaudiny J, Scheit KH, et al. (1994) The gene for the amyloid precursor-like protein APLP2 is assigned to human chromosome 11q23-q25. Genomics 20: 308–311. 8020984

50. Wasco W, Gurubhagavatula S, Paradis MD, Romano DM, Sisodia SS, et al. (1993) Isolation and characterization of APLP2 encoding a homologue of the Alzheimer's associated amyloid beta protein precursor. Nat Genet 5: 95–100. 8220435

51. Cousins SL, Dai W, Stephenson FA (2015) APLP1 and APLP2, members of the APP family of proteins, behave similarly to APP in that they associate with NMDA receptors and enhance NMDA receptor surface expression. J Neurochem.

52. Aydin D, Weyer SW, Muller UC (2012) Functions of the APP gene family in the nervous system: insights from mouse models. Exp Brain Res 217: 423–434. doi: 10.1007/s00221-011-2861-2 21931985

53. Tkatchenko AV, Walsh PA, Tkatchenko TV, Gustincich S, Raviola E (2006) Form deprivation modulates retinal neurogenesis in primate experimental myopia. Proc Natl Acad Sci U S A 103: 4681–4686. 16537371

54. Subramanian A, Kuehn H, Gould J, Tamayo P, Mesirov JP (2007) GSEA-P: a desktop application for Gene Set Enrichment Analysis. Bioinformatics 23: 3251–3253. 17644558

55. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, et al. (2005) Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 102: 15545–15550. 16199517

56. Wachtmeister L (1998) Oscillatory potentials in the retina: what do they reveal. Prog Retin Eye Res 17: 485–521. 9777648

57. Dong CJ, Agey P, Hare WA (2004) Origins of the electroretinogram oscillatory potentials in the rabbit retina. Vis Neurosci 21: 533–543. 15579219

58. Frumkes TE, Nelson R, Pflug R (1995) Functional role of GABA in cat retina: II. Effects of GABAA antagonists. Vis Neurosci 12: 651–661. 8527367

59. Green DG, Kapousta-Bruneau NV (1999) A dissection of the electroretinogram from the isolated rat retina with microelectrodes and drugs. Vis Neurosci 16: 727–741. 10431921

60. Hood DC, Birch DG (1996) Beta wave of the scotopic (rod) electroretinogram as a measure of the activity of human on-bipolar cells. J Opt Soc Am A Opt Image Sci Vis 13: 623–633. 8627419

61. Sharma S, Ball SL, Peachey NS (2005) Pharmacological studies of the mouse cone electroretinogram. Vis Neurosci 22: 631–636. 16332274

62. Sieving PA, Murayama K, Naarendorp F (1994) Push-pull model of the primate photopic electroretinogram: a role for hyperpolarizing neurons in shaping the b-wave. Vis Neurosci 11: 519–532. 8038126

63. Kapousta-Bruneau NV (2000) Opposite effects of GABA(A) and GABA(C) receptor antagonists on the b-wave of ERG recorded from the isolated rat retina. Vision Res 40: 1653–1665. 10814754

64. Dong CJ, Hare WA (2002) GABAc feedback pathway modulates the amplitude and kinetics of ERG b-wave in a mammalian retina in vivo. Vision Res 42: 1081–1087. 11997047

65. Dong CJ, Hare WA (2000) Contribution to the kinetics and amplitude of the electroretinogram b-wave by third-order retinal neurons in the rabbit retina. Vision Res 40: 579–589. 10824262

66. Lewis A, Wilson N, Stearns G, Johnson N, Nelson R, et al. (2011) Celsr3 is required for normal development of GABA circuits in the inner retina. PLoS Genet 7: e1002239. doi: 10.1371/journal.pgen.1002239 21852962

67. Young TL, Ronan SM, Drahozal LA, Wildenberg SC, Alvear AB, et al. (1998) Evidence that a locus for familial high myopia maps to chromosome 18p. Am J Hum Genet 63: 109–119. 9634508

68. Young TL, Ronan SM, Alvear AB, Wildenberg SC, Oetting WS, et al. (1998) A second locus for familial high myopia maps to chromosome 12q. Am J Hum Genet 63: 1419–1424. 9792869

69. Naiglin L, Gazagne C, Dallongeville F, Thalamas C, Idder A, et al. (2002) A genome wide scan for familial high myopia suggests a novel locus on chromosome 7q36. J Med Genet 39: 118–124. 11836361

70. Lam DS, Tam PO, Fan DS, Baum L, Leung YF, et al. (2003) Familial high myopia linkage to chromosome 18p. Ophthalmologica 217: 115–118. 12592049

71. Paluru P, Ronan SM, Heon E, Devoto M, Wildenberg SC, et al. (2003) New locus for autosomal dominant high myopia maps to the long arm of chromosome 17. Invest Ophthalmol Vis Sci 44: 1830–1836. 12714612

72. Stambolian D, Ibay G, Reider L, Dana D, Moy C, et al. (2004) Genomewide linkage scan for myopia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 22q12. Am J Hum Genet 75: 448–459. 15273935

73. Zhang Q, Guo X, Xiao X, Jia X, Li S, et al. (2005) A new locus for autosomal dominant high myopia maps to 4q22-q27 between D4S1578 and D4S1612. Mol Vis 11: 554–560. 16052171

74. Paluru PC, Nallasamy S, Devoto M, Rappaport EF, Young TL (2005) Identification of a novel locus on 2q for autosomal dominant high-grade myopia. Invest Ophthalmol Vis Sci 46: 2300–2307. 15980214

75. Stambolian D, Ciner EB, Reider LC, Moy C, Dana D, et al. (2005) Genome-wide scan for myopia in the Old Order Amish. Am J Ophthalmol 140: 469–476. 16084785

76. Zhang Q, Guo X, Xiao X, Jia X, Li S, et al. (2006) Novel locus for X linked recessive high myopia maps to Xq23-q25 but outside MYP1. J Med Genet 43: e20. 16648373

77. Nallasamy S, Paluru PC, Devoto M, Wasserman NF, Zhou J, et al. (2007) Genetic linkage study of high-grade myopia in a Hutterite population from South Dakota. Mol Vis 13: 229–236. 17327828

78. Yu ZQ, Li YB, Huang CX, Chu RY, Hu DN, et al. (2007) [A genome-wide screening for pathological myopia suggests a novel locus on chromosome 15q12–13]. Zhonghua Yan Ke Za Zhi 43: 233–238. 17605906

79. Paget S, Julia S, Vitezica ZG, Soler V, Malecaze F, et al. (2008) Linkage analysis of high myopia susceptibility locus in 26 families. Mol Vis 14: 2566–2574. 19122830

80. Ciner E, Wojciechowski R, Ibay G, Bailey-Wilson JE, Stambolian D (2008) Genomewide scan of ocular refraction in African-American families shows significant linkage to chromosome 7p15. Genet Epidemiol 32: 454–463. doi: 10.1002/gepi.20318 18293391

81. Lam CY, Tam PO, Fan DS, Fan BJ, Wang DY, et al. (2008) A genome-wide scan maps a novel high myopia locus to 5p15. Invest Ophthalmol Vis Sci 49: 3768–3778. doi: 10.1167/iovs.07-1126 18421076

82. Schache M, Chen CY, Pertile KK, Richardson AJ, Dirani M, et al. (2009) Fine mapping linkage analysis identifies a novel susceptibility locus for myopia on chromosome 2q37 adjacent to but not overlapping MYP12. Mol Vis 15: 722–730. 19365569

83. Yang Z, Xiao X, Li S, Zhang Q (2009) Clinical and linkage study on a consanguineous Chinese family with autosomal recessive high myopia. Mol Vis 15: 312–318. 19204786

84. Nishizaki R, Ota M, Inoko H, Meguro A, Shiota T, et al. (2009) New susceptibility locus for high myopia is linked to the uromodulin-like 1 (UMODL1) gene region on chromosome 21q22.3. Eye (Lond) 23: 222–229.

85. Ciner E, Ibay G, Wojciechowski R, Dana D, Holmes TN, et al. (2009) Genome-wide scan of African-American and white families for linkage to myopia. Am J Ophthalmol 147: 512–517 e512. doi: 10.1016/j.ajo.2008.09.004 19026404

86. Li YJ, Guggenheim JA, Bulusu A, Metlapally R, Abbott D, et al. (2009) An international collaborative family-based whole-genome linkage scan for high-grade myopia. Invest Ophthalmol Vis Sci 50: 3116–3127. doi: 10.1167/iovs.08-2781 19324860

87. Nakanishi H, Yamada R, Gotoh N, Hayashi H, Yamashiro K, et al. (2009) A genome-wide association analysis identified a novel susceptible locus for pathological myopia at 11q24.1. PLoS Genet 5: e1000660. doi: 10.1371/journal.pgen.1000660 19779542

88. Ma JH, Shen SH, Zhang GW, Zhao DS, Xu C, et al. (2010) Identification of a locus for autosomal dominant high myopia on chromosome 5p13.3-p15.1 in a Chinese family. Mol Vis 16: 2043–2054. 21042559

89. Kiefer AK, Tung JY, Do CB, Hinds DA, Mountain JL, et al. (2013) Genome-wide analysis points to roles for extracellular matrix remodeling, the visual cycle, and neuronal development in myopia. PLoS Genet 9: e1003299. doi: 10.1371/journal.pgen.1003299 23468642

90. Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, et al. (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467: 832–838. doi: 10.1038/nature09410 20881960

91. Hammond CJ, Snieder H, Gilbert CE, Spector TD (2001) Genes and environment in refractive error: the twin eye study. Invest Ophthalmol Vis Sci 42: 1232–1236. 11328732

92. Lyhne N, Sjolie AK, Kyvik KO, Green A (2001) The importance of genes and environment for ocular refraction and its determiners: a population based study among 20–45 year old twins. Br J Ophthalmol 85: 1470–1476. 11734523

93. Hammond CJ, Andrew T, Mak YT, Spector TD (2004) A susceptibility locus for myopia in the normal population is linked to the PAX6 gene region on chromosome 11: a genomewide scan of dizygotic twins. Am J Hum Genet 75: 294–304. 15307048

94. Slunt HH, Thinakaran G, Von Koch C, Lo AC, Tanzi RE, et al. (1994) Expression of a ubiquitous, cross-reactive homologue of the mouse beta-amyloid precursor protein (APP). J Biol Chem 269: 2637–2644. 8300594

95. Heber S, Herms J, Gajic V, Hainfellner J, Aguzzi A, et al. (2000) Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members. J Neurosci 20: 7951–7963. 11050115

96. Soba P, Eggert S, Wagner K, Zentgraf H, Siehl K, et al. (2005) Homo- and heterodimerization of APP family members promotes intercellular adhesion. EMBO J 24: 3624–3634. 16193067

97. Herms J, Anliker B, Heber S, Ring S, Fuhrmann M, et al. (2004) Cortical dysplasia resembling human type 2 lissencephaly in mice lacking all three APP family members. EMBO J 23: 4106–4115. 15385965

98. Stone RA, Laties AM, Raviola E, Wiesel TN (1988) Increase in retinal vasoactive intestinal polypeptide after eyelid fusion in primates. Proc Natl Acad Sci U S A 85: 257–260. 2448769

99. Seltner RL, Stell WK (1995) The effect of vasoactive intestinal peptide on development of form deprivation myopia in the chick: a pharmacological and immunocytochemical study. Vision Res 35: 1265–1270. 7610586

100. Fischer AJ, Seltner RL, Stell WK (1997) N-methyl-D-aspartate-induced excitotoxicity causes myopia in hatched chicks. Can J Ophthalmol 32: 373–377. 9363340

101. Fischer AJ, McGuire JJ, Schaeffel F, Stell WK (1999) Light- and focus-dependent expression of the transcription factor ZENK in the chick retina. Nat Neurosci 2: 706–712. 10412059

102. Feldkaemper MP, Schaeffel F (2002) Evidence for a potential role of glucagon during eye growth regulation in chicks. Vis Neurosci 19: 755–766. 12688670

103. Zhong X, Ge J, Smith EL 3rd, Stell WK (2004) Image defocus modulates activity of bipolar and amacrine cells in macaque retina. Invest Ophthalmol Vis Sci 45: 2065–2074. 15223778

104. Vessey KA, Lencses KA, Rushforth DA, Hruby VJ, Stell WK (2005) Glucagon receptor agonists and antagonists affect the growth of the chick eye: a role for glucagonergic regulation of emmetropization? Invest Ophthalmol Vis Sci 46: 3922–3931. 16249465

105. Chen JC, Brown B, Schmid KL (2006) Evaluation of inner retinal function in myopia using oscillatory potentials of the multifocal electroretinogram. Vision Res 46: 4096–4103. 17010409

106. Mathis U, Schaeffel F (2007) Glucagon-related peptides in the mouse retina and the effects of deprivation of form vision. Graefes Arch Clin Exp Ophthalmol 245: 267–275. 16741711

107. Feldkaemper MP, Neacsu I, Schaeffel F (2009) Insulin acts as a powerful stimulator of axial myopia in chicks. Invest Ophthalmol Vis Sci 50: 13–23. doi: 10.1167/iovs.08-1702 18599564

108. Ashby R, Kozulin P, Megaw PL, Morgan IG (2010) Alterations in ZENK and glucagon RNA transcript expression during increased ocular growth in chickens. Mol Vis 16: 639–649. 20405027

109. Wassle H, Heinze L, Ivanova E, Majumdar S, Weiss J, et al. (2009) Glycinergic transmission in the Mammalian retina. Front Mol Neurosci 2: 6. doi: 10.3389/neuro.02.006.2009 19924257

110. Werblin FS (2010) Six different roles for crossover inhibition in the retina: correcting the nonlinearities of synaptic transmission. Vis Neurosci 27: 1–8. doi: 10.1017/S0952523810000076 20392301

111. Russell TL, Werblin FS (2010) Retinal synaptic pathways underlying the response of the rabbit local edge detector. J Neurophysiol 103: 2757–2769. doi: 10.1152/jn.00987.2009 20457864

112. Zhang C, McCall MA (2012) Receptor targets of amacrine cells. Vis Neurosci 29: 11–29. doi: 10.1017/S0952523812000028 22310370

113. Buldyrev I, Taylor WR (2013) Inhibitory mechanisms that generate centre and surround properties in ON and OFF brisk-sustained ganglion cells in the rabbit retina. J Physiol 591: 303–325. doi: 10.1113/jphysiol.2012.243113 23045347

114. Buldyrev I, Puthussery T, Taylor WR (2012) Synaptic pathways that shape the excitatory drive in an OFF retinal ganglion cell. J Neurophysiol 107: 1795–1807. doi: 10.1152/jn.00924.2011 22205648

115. Venkataramani S, Van Wyk M, Buldyrev I, Sivyer B, Vaney DI, et al. (2014) Distinct roles for inhibition in spatial and temporal tuning of local edge detectors in the rabbit retina. PLoS One 9: e88560. doi: 10.1371/journal.pone.0088560 24586343

116. Gwiazda J, Thorn F, Bauer J, Held R (1993) Myopic children show insufficient accommodative response to blur. Invest Ophthalmol Vis Sci 34: 690–694. 8449687

117. Seidemann A, Schaeffel F (2003) An evaluation of the lag of accommodation using photorefraction. Vision Res 43: 419–430. 12535999

118. Smith EL 3rd, Hung LF, Huang J (2009) Relative peripheral hyperopic defocus alters central refractive development in infant monkeys. Vision Res 49: 2386–2392. doi: 10.1016/j.visres.2009.07.011 19632261

119. Boyd A, Golding J, Macleod J, Lawlor DA, Fraser A, et al. (2013) Cohort Profile: the 'children of the 90s'—the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 42: 111–127. doi: 10.1093/ije/dys064 22507743

120. Guggenheim JA, Northstone K, McMahon G, Ness AR, Deere K, et al. (2012) Time outdoors and physical activity as predictors of incident myopia in childhood: a prospective cohort study. Invest Ophthalmol Vis Sci 53: 2856–2865. doi: 10.1167/iovs.11-9091 22491403

121. Guggenheim JA, Zhou X, Evans DM, Timpson NJ, McMahon G, et al. (2013) Coordinated genetic scaling of the human eye: shared determination of axial eye length and corneal curvature. Invest Ophthalmol Vis Sci 54: 1715–1721. doi: 10.1167/iovs.12-10560 23385790

122. Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34: 816–834. doi: 10.1002/gepi.20533 21058334

123. Mattapallil MJ, Wawrousek EF, Chan CC, Zhao H, Roychoudhury J, et al. (2012) The Rd8 Mutation of the Crb1 Gene Is Present in Vendor Lines of C57BL/6N Mice and Embryonic Stem Cells, and Confounds Ocular Induced Mutant Phenotypes. Invest Ophthalmol Vis Sci 53: 2921–2927. doi: 10.1167/iovs.12-9662 22447858

124. Tkatchenko TV, Shen Y, Tkatchenko AV (2010) Analysis of postnatal eye development in the mouse with high-resolution small animal magnetic resonance imaging. Invest Ophthalmol Vis Sci 51: 21–27. doi: 10.1167/iovs.08-2767 19661239

125. Tkatchenko AV, Shen Y, Tkatchenko TV (2012) Genetic background modulates refractive eye development and susceptibility to myopia in the mouse. Invest Ophthalmol Vis Sci 53: E-Abstract 3465.

126. Tkatchenko TV, Shen Y, Braun RD, Bawa G, Kumar P, et al. (2013) Photopic visual input is necessary for emmetropization in mice. Exp Eye Res 115C: 87–95.

127. Tkatchenko TV, Tkatchenko AV (2010) Ketamine-xylazine anesthesia causes hyperopic refractive shift in mice. J Neurosci Methods 193: 67–71. doi: 10.1016/j.jneumeth.2010.07.036 20813132

128. Parssinen O, Lyyra AL (1993) Myopia and myopic progression among schoolchildren: a three-year follow-up study. Invest Ophthalmol Vis Sci 34: 2794–2802. 8344801

129. Goss DA (2000) Nearwork and myopia. Lancet 356: 1456–1457. 11081523

130. Hepsen IF, Evereklioglu C, Bayramlar H (2001) The effect of reading and near-work on the development of myopia in emmetropic boys: a prospective, controlled, three-year follow-up study. Vision Res 41: 2511–2520. 11483181

131. Saw SM, Chua WH, Hong CY, Wu HM, Chan WY, et al. (2002) Nearwork in early-onset myopia. Invest Ophthalmol Vis Sci 43: 332–339. 11818374

132. Gwiazda J, Bauer J, Thorn F, Held R (1995) A dynamic relationship between myopia and blur-driven accommodation in school-aged children. Vision Res 35: 1299–1304. 7610590

133. Abbott ML, Schmid KL, Strang NC (1998) Differences in the accommodation stimulus response curves of adult myopes and emmetropes. Ophthalmic Physiol Opt 18: 13–20. 9666906

134. Charman WN (1999) Near vision, lags of accommodation and myopia. Ophthalmic Physiol Opt 19: 126–133. 10615448

135. Gwiazda JE, Hyman L, Norton TT, Hussein ME, Marsh-Tootle W, et al. (2004) Accommodation and related risk factors associated with myopia progression and their interaction with treatment in COMET children. Invest Ophthalmol Vis Sci 45: 2143–2151. 15223788

136. Shen W, Vijayan M, Sivak JG (2005) Inducing form-deprivation myopia in fish. Invest Ophthalmol Vis Sci 46: 1797–1803. 15851585

137. Wallman J, Turkel J, Trachtman J (1978) Extreme myopia produced by modest change in early visual experience. Science 201: 1249–1251. 694514

138. Sherman SM, Norton TT, Casagrande VA (1977) Myopia in the lid-sutured tree shrew (Tupaia glis). Brain Res 124: 154–157. 843938

139. Wiesel TN, Raviola E (1977) Myopia and eye enlargement after neonatal lid fusion in monkeys. Nature 266: 66–68. 402582

140. Smith EL 3rd, Hung LF (1999) The role of optical defocus in regulating refractive development in infant monkeys. Vision Res 39: 1415–1435. 10343811

141. Howlett MH, McFadden SA (2009) Spectacle lens compensation in the pigmented guinea pig. Vision Res 49: 219–227. doi: 10.1016/j.visres.2008.10.008 18992765

142. Howlett MH, McFadden SA (2006) Form-deprivation myopia in the guinea pig (Cavia porcellus). Vision Res 46: 267–283. 16139323

143. Tkatchenko TV, Shen Y, Tkatchenko AV (2010) Mouse experimental myopia has features of primate myopia. Invest Ophthalmol Vis Sci 51: 1297–1303. doi: 10.1167/iovs.09-4153 19875658

144. Schaeffel F, Burkhardt E, Howland HC, Williams RW (2004) Measurement of refractive state and deprivation myopia in two strains of mice. Optom Vis Sci 81: 99–110. 15127929

145. Prusky GT, Alam NM, Beekman S, Douglas RM (2004) Rapid quantification of adult and developing mouse spatial vision using a virtual optomotor system. Invest Ophthalmol Vis Sci 45: 4611–4616. 15557474

146. Yang H, Wanner IB, Roper SD, Chaudhari N (1999) An optimized method for in situ hybridization with signal amplification that allows the detection of rare mRNAs. J Histochem Cytochem 47: 431–446. 10082745

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2015 Číslo 8

Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa