Reduced expression of Pax6 in lens and cornea of mutant mice leads to failure of chamber angle development and juvenile glaucoma

Human Molecular Genetics

Volumn 19, Issue 17, 2010, Pages 3332-3342

  Kroeber, Markus ^a   Davis, Noa ^b   Holzmann, Silvia ^a   Kritzenberger, Michaela ^a   Shelah Goraly, Michal ^c   Ofri, Ron ^c   Ashery Padan, Ruth ^b   Tamm, Ernst R ^a  

^a UNIVERSITY OF REGENSBURG   (Germany)

^b TEL AVIV UNIVERSITY   (Israel)

^c HEBREW UNIVERSITY OF JERUSALEM   (Israel)

Author keywords

[No Author keywords available]

Indexed keywords

CRE RECOMBINASE; TRANSCRIPTION FACTOR PAX6;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTERIOR EYE CHAMBER ANGLE; ARTICLE; AXONAL INJURY; CONTROLLED STUDY; CORNEA; CORNEA CELL; EPITHELIUM CELL; EYE DEVELOPMENT; GENE CONTROL; GENE EXPRESSION; GENE INACTIVATION; GLAUCOMA; HAPLOTYPE; INTRAOCULAR PRESSURE; IRIDOCORNEAL ANGLE; IRIS; LENS; LOXP SITE; MOUSE; MOUSE MUTANT; NERVE FIBER DEGENERATION; NONHUMAN; OPTIC DISK CUP; OPTIC NERVE; OPTIC NERVE DISEASE; PETERS ANOMALY; PRIORITY JOURNAL; SCHLEMM CANAL; TRABECULAR MESHWORK;

ANIMALS; ANTERIOR CHAMBER; CORNEA; DISEASE MODELS, ANIMAL; DOWN-REGULATION; EYE PROTEINS; FEMALE; GENE EXPRESSION; GLAUCOMA; HOMEODOMAIN PROTEINS; HUMANS; LENS, CRYSTALLINE; MALE; MICE; MICE, KNOCKOUT; PAIRED BOX TRANSCRIPTION FACTORS; REPRESSOR PROTEINS; SEQUENCE DELETION;

MUS;

EID: 77955387940     PISSN: 09646906     EISSN: 14602083     Source Type: Journal    
DOI: 10.1093/hmg/ddq237     Document Type: Article

References (90)

1. Gehring, W.J. (2002) The genetic control of eye development and its implications for the evolution of the various eye-types. Int. J. Dev. Biol., 46, 65-73.
2. Ashery-Padan, R. and Gruss, P. (2001) Pax6 lights-up the way for eye development. Curr. Opin. Cell Biol., 13, 706-714.
3. Chow, R.L. and Lang, R.A. (2001) Early eye development in vertebrates. Annu. Rev. Cell Dev. Biol., 17, 255-296.
4. Kozmik, Z. (2008) The role of Pax genes in eye evolution. Brain Res. Bull., 75, 335-339.
5. Mintz-Hittner, H.A. (1996) Aniridia. In Ritch, R., Shields, M.B. and Krupin, T. (eds), The Glaucomas. Mosby, St Louis, pp. 859-874.
6. Brauner, S.C., Walton, D.S. and Chen, T.C. (2008) Aniridia. Int. Ophthalmol. Clin., 48, 79-85.
7. Lee, H., Khan, R. and O'Keefe, M. (2008) Aniridia: current pathology and management. Acta Ophthalmol. (Copenh.), 86, 708-715.
8. Prosser, J. and van Heyningen, V. (1998) PAX6 mutations reviewed. Hum. Mutat., 11, 93-108.
9. Cvekl, A. and Tamm, E.R. (2004) Anterior eye development and ocular mesenchyme: new insights from mouse models and human diseases. Bioessays, 26, 374-386.
10. Hogan, B.L., Hirst, E.M., Horsburgh, G. and Hetherington, C.M. (1988) Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities. Development, 103 (suppl.), 115-119.
11. Glaser, T., Lane, J. and Housman, D. (1990) A mouse model of the aniridia-Wilms tumor deletion syndrome. Science, 250, 823-827.
12. Theiler, K. and Varnum, D.S. (1981) Development of coloboma (Cm/+), a mutation with anterior lens adhesion. Anat. Embryol. (Berl.), 162, 121-126.
13. Theiler, K., Varnum, D.S. and Stevens, L.C. (1978) Development of Dickie's small eye, a mutation in the house mouse. Anat. Embryol. (Berl.), 155, 81-86.
14. Johnson, M. (2006) What controls aqueous humour outflow resistance?. Exp. Eye Res., 82, 545-557.
15. Tamm, E.R. (2009) The trabecular meshwork outflow pathways: structural and functional aspects. Exp. Eye Res., 88, 648-655.
16. Baulmann, D., Ohlmann, A., Flügel-Koch, C., Goswami, S., Cvekl, A. and Tamm, E.R. (2002) Pax6 heterozygous eyes show defects in chamber angle differentiation that are associated with a wide spectrum of other anterior eye segment abnormalities. Mech. Dev., 118, 3-17.
17. Grindley, J.C., Davidson, D.R. and Hill, R.E. (1995) The role of pax-6 in eye and nasal development. Development, 121, 1433-1442.
18. Walther, C. and Gruss, P. (1991) Pax-6, a murine paired box gene, is expressed in the developing CNS. Development, 113, 1435-1449.
19. Koroma, B.M., Yang, J.M. and Sundin, O.H. (1997) The Pax-6 homeobox gene is expressed throughout the corneal and conjunctival epithelia. Invest. Ophthalmol. Vis. Sci., 38, 108-120.
20. Nishina, S., Kohsaka, S., Yamaguchi, Y., Handa, H., Kawakami, A., Fujisawa, H. and Azuma, N. (1999) PAX6 expression in the developing human eye. Br. J. Ophthalmol., 83, 723-727.
21. Tamm, E.R. (2004) Genetic changes and their influence on structure and function of the eye in glaucoma. In Grehn, F.J. and Stamper, R. (eds), Essentials in Opthalmology. Glaucoma. Springer, Berlin, Heidelberg, NY.
22. Ramaesh, T., Collinson, J.M., Ramaesh, K., Kaufman, M.H., West, J.D. and Dhillon, B. (2003) Corneal abnormalities in Pax6+/- small eye mice mimic human aniridia-related keratopathy. Invest. Ophthalmol. Vis. Sci., 44, 1871-1878.
23. Kanakubo, S., Nomura, T., Yamamura, K., Miyazaki, J., Tamai, M. and Osumi, N. (2006) Abnormal migration and distribution of neural crest cells in Pax6 heterozygous mutant eye, a model for human eye diseases. Genes Cells, 11, 919-933.
24. Davis-Silberman, N., Kalich, T., Oron-Karni, V., Marquardt, T., Kroeber, M., Tamm, E.R. and Ashery-Padan, R. (2005) Genetic dissection of Pax6 dosage requirements in the developing mouse eye. Hum. Mol. Genet., 14, 2265-2276.
25. Kammandel, B., Chowdhury, K., Stoykova, A., Aparicio, S., Brenner, S. and Gruss, P. (1999) Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity. Dev. Biol., 205, 79-97.
26. Griffin, C., Kleinjan, D.A., Doe, B. and van Heyningen, V. (2002) New 3′ elements control Pax6 expression in the developing pretectum, neural retina and olfactory region. Mech. Dev., 112, 89-100.
27. Kleinjan, D.A., Seawright, A., Mella, S., Carr, C.B., Tyas, D.A., Simpson, T.I., Mason, J.O., Price, D.J. and van Heyningen, V. (2006) Long-range downstream enhancers are essential for Pax6 expression. Dev. Biol., 299, 563-581.
28. Morgan, R. (2004) Conservation of sequence and function in the Pax6 regulatory elements. Trends Genet., 20, 283-287.
29. Dimanlig, P.V., Faber, S.C., Auerbach, W., Makarenkova, H.P. and Lang, R.A. (2001) The upstream ectoderm enhancer in Pax6 has an important role in lens induction. Development, 128, 4415-4424.
30. Ethier, C.R. (2002) The inner wall of Schlemm's canal. Exp. Eye Res., 74, 161-172.
31. Marquardt, T., Ashery-Padan, R., Andrejewski, N., Scardigli, R., Guillemot, F. and Gruss, P. (2001) Pax6 is required for the multipotent state of retinal progenitor cells. Cell, 105, 43-55.
32. Do, C.W. and Civan, M.M. (2009) Species variation in biology and physiology of the ciliary epithelium: similarities and differences. Exp. Eye Res., 88, 631-640.
33. Overby, D.R., Stamer, W.D. and Johnson, M. (2009) The changing paradigm of outflow resistance generation: towards synergistic models of the JCT and inner wall endothelium. Exp. Eye Res., 88, 656-670.
34. Alm, A. and Nilsson, S.F. (2009) Uveoscleral outflow-a review. Exp. Eye Res., 88, 760-768.
35. Tamm, E.R. and Kellenberger, A. (2008) Aqueous humor dynamics and trabecular meshwork. In Chalupa, L.M. and Williams, R.W. (eds), Eye, Retina, and Visual System of the Mouse. MIT Press, Cambridge, pp. 129-134.
36. Aihara, M., Lindsey, J.D. and Weinreb, R.N. (2003) Aqueous humor dynamics in mice. Invest. Ophthalmol. Vis. Sci., 44, 5168-5173.
37. The AGIS Investigators. (2000) The advanced glaucoma intervention study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am. J. Ophthalmol., 130, 429-440.
38. Collaborative Normal-Tension Glaucoma Study Group. (1998) The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Collaborative Normal-Tension Glaucoma Study Group. Am. J. Ophthalmol., 126, 498-505.
39. Leske, M.C., Heijl, A., Hussein, M., Bengtsson, B., Hyman, L. and Komaroff, E. (2003) Factors for glaucoma progression and the effect of treatment: the early manifest glaucoma trial. Arch. Ophthalmol., 121, 48-56.
40. Collaborative Normal-Tension Glaucoma Study Group. (1998) Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am. J. Ophthalmol., 126, 487-497.
41. Higginbotham, E.J., Gordon, M.O., Beiser, J.A., Drake, M.V., Bennett, G.R., Wilson, M.R. and Kass, M.A. (2004) The Ocular Hypertension Treatment Study: topical medication delays or prevents primary open-angle glaucoma in African American individuals. Arch. Ophthalmol., 122, 813-820.
42. Gordon, M.O., Beiser, J.A., Brandt, J.D., Heuer, D.K., Higginbotham, E.J., Johnson, C.A., Keltner, J.L., Miller, J.P., Parrish, R.K. 2nd, Wilson, M.R. et al. (2002) The Ocular Hypertension Treatment Study: baseline factors that predict the onset of primary open-angle glaucoma. Arch. Ophthalmol., 120, 714-720; discussion 829-730.
43. Anderson, M.G., Smith, R.S., Hawes, N.L., Zabaleta, A., Chang, B., Wiggs, J.L. and John, S.W. (2002) Mutations in genes encoding melanosomal proteins cause pigmentary glaucoma in DBA/2J mice. Nat. Genet., 30, 81-85.
44. Senatorov, V., Malyukova, I., Fariss, R., Wawrousek, E.F., Swaminathan, S., Sharan, S.K. and Tomarev, S. (2006) Expression of mutated mouse myocilin induces open-angle glaucoma in transgenic mice. J. Neurosci., 26, 11903-11914.
45. Howell, G.R., Libby, R.T. and John, S.W. (2008) Mouse genetic models: an ideal system for understanding glaucomatous neurodegeneration and neuroprotection. Prog. Brain Res., 173, 303-321.
46. Gould, D.B., Marchant, J.K., Savinova, O.V., Smith, R.S. and John, S.W. (2007) Col4a1 mutation causes endoplasmic reticulum stress and genetically modifiable ocular dysgenesis. Hum. Mol. Genet., 16, 798-807.
47. Dangata, Y.Y., Findlater, G.S., Dhillon, B. and Kaufman, M.H. (1994) Morphometric study of the optic nerve of adult normal mice and mice heterozygous for the small eye mutation (Sey/+). J. Anat., 185 (Pt 3), 627-635.
48. Howell, G.R., Libby, R.T., Jakobs, T.C., Smith, R.S., Phalan, F.C., Barter, J.W., Barbay, J.M., Marchant, J.K., Mahesh, N., Porciatti, V. et al. (2007) Axons of retinal ganglion cells are insulted in the optic nerve early in DBA/2J glaucoma. J. Cell Biol., 179, 1523-1537.
49. Grant, W.M. and Walton, D.S. (1974) Progressive changes in the angle in congenital aniridia, with development of glaucoma. Am. J. Ophthalmol., 78, 842-847.
50. Margo, C.E. (1983) Congenital aniridia: a histopathologic study of the anterior segment in children. J. Pediatr. Ophthalmol. Strabismus, 20, 192-198.
51. Ton, C.C., Miwa, H. and Saunders, G.F. (1992) Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene. Genomics, 13, 251-256.
52. Jordan, T., Hanson, I., Zaletayev, D., Hodgson, S., Prosser, J., Seawright, A., Hastie, N. and van Heyningen, V. (1992) The human PAX6 gene is mutated in two patients with aniridia. Nat. Genet., 1, 328-332.
53. Collins, T. (1893) Congenital defects of the iris and glaucoma. Trans. Ophthalmol. Soc. UK, 13, 128-139.
54. Bergmeister, R. (1904) Zwei Fälle von angeborener Irideremie. Graefes Arch. Clin. Exp. Ophthalmol., 59, 31-45.
55. Callahan, A. (1949) Aniridia with ectopia lentis and secondary glaucoma. Am. J. Ophthalmol., 32, 28-40.
56. Duke-Elder, S. (1964) Hypoplasia of the iris: aniridia. In Duke-Elder, S. (ed.), System of Ophthalmology. Vol. 3. Normal and Abnormal Development. Part 2: Congenital Disorders. Henry Kimpton, London, pp. 565-572.
57. Townsend, D.J. and Brubaker, R.F. (1980) Immediate effect of epinephrine on aqueous formation in the normal eye as measured by fluorophotometry. Invest. Ophthalmol. Vis. Sci., 196, 256-266.
58. Mishima, H.K., Kiuchi, Y., Takamatsu, M., Racz, P. and Bito, L.Z. (1997) Circadian intraocular pressure management with latanoprost: diurnal and nocturnal intraocular pressure reduction and increased uveoscleral outflow. Surv. Ophthalmol., 41 (Suppl. 2), S139-S144.
59. Toris, C.B., Camras, C.B. and Yablonski, M.E. (1999) Acute versus chronic effects of brimonidine on aqueous humor dynamics in ocular hypertensive patients. Am. J. Ophthalmol., 128, 8-14.
60. Hingorani, M., Williamson, K.A., Moore, A.T. and van Heyningen, V. (2009) Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations. Invest. Ophthalmol. Vis. Sci., 50, 2581-2590.
61. Collinson, J.M., Quinn, J.C., Buchanan, M.A., Kaufman, M.H., Wedden, S.E., West, J.D. and Hill, R.E. (2001) Primary defects in the lens underlie complex anterior segment abnormalities of the Pax6 heterozygous eye. Proc. Natl Acad. Sci. USA, 98, 9688-9693.
62. van Raamsdonk, C.D. and Tilghman, S.M. (2000) Dosage requirement and allelic expression of PAX6 during lens placode formation. Development, 127, 5439-5448.
63. Semina, E.V., Murray, J.C., Reiter, R., Hrstka, R.F. and Graw, J. (2000) Deletion in the promoter region and altered expression of Pitx3 homeobox gene in aphakia mice. Hum. Mol. Genet., 9, 1575-1585.
64. Rieger, D.K., Reichenberger, E., McLean, W., Sidow, A. and Olsen, B.R. (2001) A double-deletion mutation in the Pitx3 gene causes arrested lens development in aphakia mice. Genomics, 72, 61-72.
65. Varnum, D.S. and Stevens, L.C. (1968) Aphakia, a new mutation in the mouse. J. Hered., 59, 147-150.
66. Medina-Martinez, O., Brownell, I., Amaya-Manzanares, F., Hu, Q., Behringer, R.R. and Jamrich, M. (2005) Severe defects in proliferation and differentiation of lens cells in Foxe3 null mice. Mol. Cell Biol., 25, 8854-8863.
67. Blixt, A., Landgren, H., Johansson, B.R. and Carlsson, P. (2007) Foxe3 is required for morphogenesis and differentiation of the anterior segment of the eye and is sensitive to Pax6 gene dosage. Dev. Biol., 302, 218-229.
68. Yoshimoto, A., Saigou, Y., Higashi, Y. and Kondoh, H. (2005) Regulation of ocular lens development by Smad-interacting protein 1 involving Foxe3 activation. Development, 132, 4437-4448.
69. Wurm, A., Sock, E., Fuchshofer, R., Wegner, M. and Tamm, E.R. (2008) Anterior segment dysgenesis in the eyes of mice deficient for the high-mobility-group transcription factor Sox11. Exp. Eye Res., 86, 895-907.
70. Hanson, I.M., Fletcher, J.M., Jordan, T., Brown, A., Taylor, D., Adams, R.J., Punnett, H.H. and van, H.V. (1994) Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nat. Genet., 6, 168-173.
71. Wolf, L.V., Yang, Y., Wang, J., Xie, Q., Braunger, B., Tamm, E.R., Zavadil, J. and Cvekl, A. (2009) Identification of pax6-dependent gene regulatory networks in the mouse lens. PLoS One, 4, e4159.
72. Helbig, H., Kittredge, K.L., Coca-Prados, M., Davis, J., Palestine, A.G. and Nussenblatt, R.B. (1991) Mammalian ciliary-body epithelial cells in culture produce transforming growth factor-beta. Graefes Arch. Clin. Exp. Ophthalmol., 229, 84-87.
73. Allen, J.B., Davidson, M.G., Nasisse, M.P., Fleisher, L.N. and McGahan, M.C. (1998) The lens influences aqueous humor levels of transforming growth factor-beta 2. Graefes Arch. Clin. Exp. Ophthalmol., 236, 305-311.
74. Gordon-Thomson, C., de Iongh, R.U., Hales, A.M., Chamberlain, C.G. and McAvoy, J.W. (1998) Differential cataractogenic potency of TGF-beta1, -beta2 and -beta3 and their expression in the postnatal rat eye. Invest. Ophthalmol. Vis. Sci., 39, 1399-1409.
75. Wallentin, N., Wickstrom, K. and Lundberg, C. (1998) Effect of cataract surgery on aqueous TGF-beta and lens epithelial cell proliferation. Invest. Ophthalmol. Vis. Sci., 39, 1410-1418.
76. Granstein, R.D., Staszewski, R., Knisley, T.L., Zeira, E., Nazareno, R., Latina, M. and Albert, D.M. (1990) Aqueous humor contains transforming growth factor-β and a small (<3500 Daltons) inhibitor of thymocyte proliferation. J. Immunol., 144, 3021-3027.
77. Jampel, H.D., Roche, N., Stark, W.J. and Roberts, A.B. (1990) Transforming growth factor-β in human aqueous humor. Curr. Eye Res., 9, 963-969.
78. Cousins, S.W., McCabe, M.M., Danielpour, D. and Streilein, J.W. (1991) Identification of transforming growth factor-beta as an immunosuppressive factor in aqueous humor. Invest. Ophthalmol. Vis. Sci., 32, 2201-2211.
79. Streilein, J.W., Ksander, B.R. and Taylor, A.W. (1997) Immune deviation in relation to ocular immune privilege. J. Immunol., 158, 3557-3560.
80. Streilein, J.W. (1999) Immunoregulatory mechanisms of the eye. Prog. Retin. Eye Res., 18, 357-370.
81. Fuchshofer, R. and Tamm, E.R. (2009) Modulation of extracellular matrix turnover in the trabecular meshwork. Exp. Eye Res., 88, 683-688.
82. Iwao, K., Inatani, M., Matsumoto, Y., Ogata-Iwao, M., Takihara, Y., Irie, F., Yamaguchi, Y., Okinami, S. and Tanihara, H. (2009) Heparan sulfate deficiency leads to Peters anomaly in mice by disturbing neural crest TGF-beta2 signaling. J. Clin. Invest., 119, 1997-2008.
83. Saika, S., Liu, C.Y., Azhar, M., Sanford, L.P., Doetschman, T., Gendron, R.L., Kao, C.W. and Kao, W.W. (2001) TGFbeta2 in corneal morphogenesis during mouse embryonic development. Dev. Biol., 240, 419-432.
84. Sanford, L.P., Ormsby, I., Gittenberger-de Groot, A.C., Sariola, H., Friedman, R., Boivin, G.P., Cardell, E.L. and Doetschman, T. (1997) TGFbeta2 knockout mice have multiple developmental defects that are non-overlapping with other TGFbeta knockout phenotypes. Development, 124, 2659-2670.
85. Ashery-Padan, R., Marquardt, T., Zhou, X. and Gruss, P. (2000) Pax6 activity in the lens primordium is required for lens formation and for correct placement of a single retina in the eye. Genes Dev., 14, 2701-2711.
86. Karnovsky, M.J. (1965) A formaldehyde-glutaraldehyde fixative of high osmolality for use in electron-microscopy. J. Cell Biol., 27, 137-138.
87. Richardson, K.C., Jarret, L. and Finke, H. (1960) Embedding in epoxy resins for ultrathin sectioning in electron microscopy. Stain Technol., 35, 313-323.
88. Schultze, W.H. (1972) Über das Paraphenylendiamin in der histologischen Färbetechnik und über eine neue Schnellfärbemethode der Nervenmarkscheide am Gefrierschnitt. Zentralbl. Pathol., 36, 639-640.
89. John, S.W., Hagaman, J.R., MacTaggart, T.E., Peng, L. and Smithes, O. (1997) Intraocular pressure in inbred mouse strains. Invest. Ophthalmol. Vis. Sci., 38, 249-253.
90. Zillig, M., Wurm, A., Grehn, F.J., Russell, P. and Tamm, E.R. (2005) Overexpression and properties of wild-type and Tyr437His mutated myocilin in the eyes of transgenic mice. Invest. Ophthalmol. Vis. Sci., 46, 223-234.