title: Further analysis of the lens of ephrin-A5-/- mice: development of postnatal defects.
abstract: OBJECTIVE
  The cells of the mammalian lens must be carefully organized and regulated to maintain clarity. Recent studies have identified the Eph receptor ligand ephrin-A5 as a major contributor to lens development, as mice lacking ephrin-A5 develop abnormal lenses, resulting in cataracts. As a follow-up to our previous study on the cataracts observed in ephrin-A5(-/-) animals, we have further examined the morphological and molecular changes in the ephrin-A5(-/-) lens.
  
  
  METHODS
  Wild-type and ephrin-A5(-/-) eyes at various ages were fixed, sectioned, and examined using histological techniques. Protein expression and localization were determined using immunohistochemistry and western blot analysis.
  
  
  RESULTS
  Lens abnormalities in the ephrin-A5(-/-) animals are observed at postnatal stages, with lens opacity occurring by postnatal day 21. Structural defects in the lens are first observed in the outer lens fiber cell region where cells in the ephrin-A5(-/-) lens are severely disorganized. Ephrin-A5 and the Eph receptor EphA2 are expressed during early ocular development and continue to be expressed into postnatal stages. The cataracts in the ephrin-A5(-/-) mutants occur regardless of the presence of the CP49 mutation.
  
  
  CONCLUSIONS
  In this follow-up study, we have uncovered additional details explicating the mechanisms underlying ephrin-A5 function in the lens. Furthermore, elucidation of the expression of ephrin-A5 and the Eph receptor EphA2 in the lens supports a fundamental role for this receptor-ligand complex in lens development. These observations, in concert with our previous study, strongly suggest that ephrin-A5 has a critical role in postnatal lens fiber organization to maintain lens transparency.
authors: Department of Chemical Biology, Susan Lehman-Cullman Laboratory for Cancer Research, Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
authors: Alexander I
authors: AI
authors: Son
authors: Margaret A
authors: MA
authors: Cooper
authors: Michal
authors: M
authors: Sheleg
authors: Yuhai
authors: Y
authors: Sun
authors: Norman J
authors: NJ
authors: Kleiman
authors: Renping
authors: R
authors: Zhou
mesh_terms: D000818:Animals; D002386:Cataract / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D036386:Ephrin-A5 / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007381:Intermediate Filament Proteins / Q000235:genetics / Q000378:metabolism; D007908:Lens, Crystalline / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D036104:Receptor, EphA2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012720:Severity of Illness Index
chemical_list: D036386:Ephrin-A5; D005136:Eye Proteins; D007381:Intermediate Filament Proteins; C084808:phakinin; D036104:Receptor, EphA2
references: Bull Soc Belge Ophtalmol. 2000;(278):55-9
references: 11761562
references: Exp Eye Res. 2009 Feb;88(2):133-9
references: 18840431
references: Invest Ophthalmol Vis Sci. 2012 Feb 01;53(2):551-9
references: 22167091
references: Nat Neurosci. 2004 Jan;7(1):33-40
references: 14699416
references: J Membr Biol. 2007 Mar;216(1):1-16
references: 17568975
references: J Gen Physiol. 2004 Oct;124(4):289-300
references: 15452195
references: Exp Eye Res. 2002 Jun;74(6):753-60
references: 12126948
references: Neurosci Bull. 2007 Sep;23(5):249-55
references: 17952132
references: J Cell Sci. 2000 May;113 ( Pt 10):1793-802
references: 10769210
references: Exp Eye Res. 2004 Mar;78(3):673-87
references: 15106947
references: Anat Embryol (Berl). 1999 Oct;200(4):403-11
references: 10460477
references: PLoS Genet. 2009 Jul;5(7):e1000584
references: 19649315
references: Mol Vis. 2010 Mar 24;16:511-7
references: 20361013
references: Neuron. 1998 Feb;20(2):235-43
references: 9491985
references: Sci China Life Sci. 2012 May;55(5):434-43
references: 22645087
references: Mol Vis. 2011;17:1553-8
references: 21686326
references: J Cell Sci. 2003 Dec 15;116(Pt 24):4985-95
references: 14625392
references: Nat Rev Mol Cell Biol. 2005 Aug;6(8):622-34
references: 16025097
references: Philos Trans R Soc Lond B Biol Sci. 2011 Apr 27;366(1568):1219-33
references: 21402582
references: Physiol Rev. 2010 Jan;90(1):179-206
references: 20086076
references: Dev Biol. 2008 Jul 15;319(2):298-308
references: 18514185
references: Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16620-5
references: 18948590
references: J Cell Biol. 1983 Nov;97(5 Pt 1):1491-9
references: 6355119
references: Mol Vis. 2008;14:2042-55
references: 19005574
references: Hum Mutat. 2009 May;30(5):E603-11
references: 19306328
references: Invest Ophthalmol Vis Sci. 1997 Aug;38(9):1678-87
references: 9286256
references: J Cell Sci. 2008 Feb 1;121(Pt 3):358-68
references: 18198190
references: Nat Rev Cancer. 2010 Mar;10(3):165-80
references: 20179713
references: Cell. 1995 Aug 11;82(3):371-81
references: 7634327
references: Nat Neurosci. 2004 May;7(5):501-9
references: 15107857
references: J Cell Sci. 2011 Jan 15;124(Pt 2):198-206
references: 21172802
references: J Neurosci. 1996 Nov 15;16(22):7182-92
references: 8929427
references: J Cell Sci. 2009 May 15;122(Pt 10):1607-15
references: 19401333
references: Exp Eye Res. 2004 Apr;78(4):875-89
references: 15037121
references: Nat Rev Mol Cell Biol. 2005 Jun;6(6):462-75
references: 15928710
references: Biochim Biophys Acta. 2011 Sep;1812(9):1089-97
references: 21511033
references: Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1396-410
references: 8641842
references: Mol Biol Cell. 2009 Apr;20(7):1949-59
references: 19193766
references: Invest Ophthalmol Vis Sci. 1996 Oct;37(11):2276-84
references: 8843924
references: PLoS One. 2011;6(11):e28147
references: 22140528
references: Nature. 1999 Jul 1;400(6739):77-81
references: 10403252
references: J Cell Biol. 1989 Jun;108(6):2255-75
references: 2738093
references: Cell Growth Differ. 1999 Sep;10(9):629-38
references: 10511313
references: Dev Biol. 2011 Jan 15;349(2):363-77
references: 20969840
references: Invest Ophthalmol Vis Sci. 2000 Mar;41(3):859-63
references: 10711704
references: Invest Ophthalmol Vis Sci. 2004 Mar;45(3):884-91
references: 14985306
references: Prog Biophys Mol Biol. 2004 Nov;86(3):407-85
references: 15302206
references: Exp Eye Res. 2000 Jun;70(6):767-76
references: 10843781
references: Biochim Biophys Acta. 2009 Oct;1790(10):1095-108
references: 19463898
references: J Cell Biol. 1997 Apr 7;137(1):37-49
references: 9105035
references: Nat Cell Biol. 2011 Jul 31;13(9):1100-7
references: 21804545
references: J Comp Neurol. 2009 Jun 1;514(4):310-28
references: 19326470
references: Development. 2006 Dec;133(24):4839-47
references: 17108003