title: Glaucoma: genes, phenotypes, and new directions for therapy.
abstract: Glaucoma, a leading cause of blindness worldwide, is characterized by progressive optic nerve damage, usually associated with intraocular pressure. Although the clinical progression of the disease is well defined, the molecular events responsible for glaucoma are currently poorly understood and current therapeutic strategies are not curative. This review summarizes the human genetics and genomic approaches that have shed light on the complex inheritance of glaucoma genes and the potential for gene-based and cellular therapies that this research makes possible.
authors.affiliation: Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Bao Jian
authors.initials: BJ
authors.lastname: Fan
authors.forename: Janey L
authors.initials: JL
authors.lastname: Wiggs
mesh_terms: D001766:Blindness / Q000235:genetics / Q000628:therapy; D018450:Disease Progression; D005123:Eye / Q000033:anatomy & histology / Q000473:pathology; D005544:Forecasting; D008040:Genetic Linkage; D005901:Glaucoma / Q000188:drug therapy / Q000235:genetics* / Q000628:therapy*; D006801:Humans; D007429:Intraocular Pressure; D009900:Optic Nerve / Q000473:pathology; D010641:Phenotype; D014065:Tonometry, Ocular
references.citation: Clin Biochem. 2006 Mar;39(3):231-9
references.pmid: 16412407
references.citation: Nat Genet. 1998 May;19(1):47-50
references.pmid: 9590287
references.citation: Arch Ophthalmol. 2001 Nov;119(11):1674-8
references.pmid: 11709019
references.citation: Exp Eye Res. 2009 Apr;88(4):704-12
references.pmid: 18804106
references.citation: Invest Ophthalmol Vis Sci. 2008 Apr;49(4):1459-63
references.pmid: 18385063
references.citation: Surv Ophthalmol. 2007 Nov;52 Suppl 2:S155-61
references.pmid: 17998041
references.citation: Invest Ophthalmol Vis Sci. 2006 Jun;47(6):2542-6
references.pmid: 16723468
references.citation: Mol Ther. 2010 Mar;18(3):491-501
references.pmid: 19953083
references.citation: Hum Genet. 2003 May;112(5-6):600-9
references.pmid: 12616399
references.citation: Hum Mol Genet. 1996 Aug;5(8):1199-203
references.pmid: 8842741
references.citation: Arch Ophthalmol. 2010 Apr;128(4):466-71
references.pmid: 20385943
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 11;106(32):13469-74
references.pmid: 19805021
references.citation: Invest Ophthalmol Vis Sci. 2008 Jun;49(6):2773-80
references.pmid: 18281610
references.citation: Lancet. 2009 Nov 7;374(9701):1597-605
references.pmid: 19854499
references.citation: Arch Ophthalmol. 2007 Jan;125(1):86-92
references.pmid: 17210857
references.citation: Mol Vis. 2008 Sep 05;14:1659-65
references.pmid: 18776954
references.citation: Invest Ophthalmol Vis Sci. 2010 Jan;51(1):327-34
references.pmid: 19710411
references.citation: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3209-15
references.pmid: 17591890
references.citation: Arch Ophthalmol. 2008 Mar;126(3):420-1
references.pmid: 18332326
references.citation: Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4453-7
references.pmid: 18586872
references.citation: Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5275-80
references.pmid: 19458335
references.citation: Br J Ophthalmol. 2006 Dec;90(12):1505-9
references.pmid: 16825280
references.citation: Mol Vis. 2004 Nov 09;10:851-6
references.pmid: 15547491
references.citation: Genomics. 1995 Nov 20;30(2):171-7
references.pmid: 8586416
references.citation: Arch Ophthalmol. 1999 Feb;117(2):237-41
references.pmid: 10037570
references.citation: Trans Am Ophthalmol Soc. 2009 Dec;107:127-33
references.pmid: 20126489
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12838-42
references.pmid: 19625618
references.citation: Nat Genet. 1993 May;4(1):47-50
references.pmid: 8513321
references.citation: Mol Vis. 2010 Apr 21;16:705-12
references.pmid: 20431720
references.citation: Invest Ophthalmol Vis Sci. 2008 May;49(5):1932-9
references.pmid: 18436825
references.citation: Clin Genet. 2002 Feb;61(2):79-88
references.pmid: 11940081
references.citation: Hum Mol Genet. 2002 May 15;11(10):1161-7
references.pmid: 12015275
references.citation: Hum Mol Genet. 1997 Apr;6(4):641-7
references.pmid: 9097971
references.citation: Mol Vis. 2002 Apr 24;8:127-9
references.pmid: 12011806
references.citation: J Glaucoma. 2005 Aug;14(4):318-20
references.pmid: 15990617
references.citation: Am J Hum Genet. 1996 Jan;58(1):243-4
references.pmid: 8554064
references.citation: Mol Vis. 2006 Feb 14;12:85-92
references.pmid: 16518310
references.citation: Am J Hum Genet. 2009 May;84(5):664-71
references.pmid: 19361779
references.citation: Am J Hum Genet. 1998 Nov;63(5):1549-52
references.pmid: 9792882
references.citation: Arch Ophthalmol. 1997 Mar;115(3):384-8
references.pmid: 9076212
references.citation: Invest Ophthalmol Vis Sci. 2010 Jun;51(6):3029-41
references.pmid: 20089870
references.citation: Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17105-10
references.pmid: 19805132
references.citation: Am J Hum Genet. 1996 Sep;59(3):613-9
references.pmid: 8751862
references.citation: Invest Ophthalmol Vis Sci. 2010 Jan;51(1):236-48
references.pmid: 19684004
references.citation: Stem Cells. 2010 Apr;28(4):695-703
references.pmid: 20166150
references.citation: Exp Eye Res. 2010 Jul;91(1):48-53
references.pmid: 20394744
references.citation: Eye (Lond). 2000 Jun;14 ( Pt 3B):422-8
references.pmid: 11026969
references.citation: Hum Mol Genet. 2008 Aug 15;17(16):2474-85
references.pmid: 18469340
references.citation: Graefes Arch Clin Exp Ophthalmol. 2006 Aug;244(8):984-90
references.pmid: 16411107
references.citation: Expert Rev Mol Med. 2005 Nov 08;7(25):1-17
references.pmid: 16274491
references.citation: Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1820-7
references.pmid: 12036985
references.citation: Ophthalmology. 2009 Jul;116(7):1243-9
references.pmid: 19450880
references.citation: Genomics. 1996 Aug 15;36(1):142-50
references.pmid: 8812425
references.citation: J Glaucoma. 2006 Jun;15(3):218-22
references.pmid: 16778644
references.citation: Arch Ophthalmol. 2007 Jan;125(1):30-7
references.pmid: 17210849
references.citation: Invest Ophthalmol Vis Sci. 2010 Jun;51(6):2968-75
references.pmid: 20107165
references.citation: J Glaucoma. 2009 Jan;18(1):73-8
references.pmid: 19142139
references.citation: Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5712-7
references.pmid: 19553612
references.citation: Invest Ophthalmol Vis Sci. 2004 Jan;45(1):59-62
references.pmid: 14691154
references.citation: Hum Mol Genet. 2010 Jul 1;19(13):2716-24
references.pmid: 20395239
references.citation: Nat Genet. 1996 Dec;14(4):392-9
references.pmid: 8944018
references.citation: Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4357-65
references.pmid: 14507880
references.citation: BMC Med Genet. 2008 Feb 06;9:5
references.pmid: 18254956
references.citation: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3262-7
references.pmid: 16877390
references.citation: Am J Hum Genet. 1997 Feb;60(2):296-304
references.pmid: 9012402
references.citation: Science. 1997 Jan 31;275(5300):668-70
references.pmid: 9005853
references.citation: Ophthalmology. 2010 Feb;117(2):267-74
references.pmid: 19969364
references.citation: Neuroscience. 2009 Aug 18;162(2):375-82
references.pmid: 19422885
references.citation: Hum Mol Genet. 2008 Mar 1;17(5):710-6
references.pmid: 18037624
references.citation: Am J Hum Genet. 2004 Jun;74(6):1314-20
references.pmid: 15108121
references.citation: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5368-75
references.pmid: 17122126
references.citation: Ophthalmology. 2007 Jan;114(1):10-9
references.pmid: 17095090
references.citation: Hum Genet. 2008 Jan;122(6):589-93
references.pmid: 17924146
references.citation: Am J Hum Genet. 1998 Nov;63(5):1316-28
references.pmid: 9792859
references.citation: Am J Med Genet. 2002 Aug 1;111(2):182-6
references.pmid: 12210347
references.citation: Science. 2003 Mar 7;299(5612):1578-81
references.pmid: 12624268
references.citation: Invest Ophthalmol Vis Sci. 2007 Apr;48(4):1607-14
references.pmid: 17389490
references.citation: Mol Vis. 2006 Jun 12;12:673-80
references.pmid: 16785856
references.citation: Science. 2007 Sep 7;317(5843):1397-400
references.pmid: 17690259
references.citation: Mol Vis. 2009 Jun 04;15:1120-6
references.pmid: 19503743
references.citation: Mol Vis. 2007 May 23;13:779-84
references.pmid: 17563728
references.citation: Mol Diagn. 2004;8(4):245-52
references.pmid: 15887980
references.citation: Eye (Lond). 2008 Jun;22(6):838-43
references.pmid: 17293784
references.citation: Arch Ophthalmol. 2007 Jan;125(1):74-9
references.pmid: 17210855
references.citation: Invest Ophthalmol Vis Sci. 2005 Jun;46(6):2002-5
references.pmid: 15914615
references.citation: Surv Ophthalmol. 2009 Jul-Aug;54(4):472-86
references.pmid: 19539835
references.citation: BMC Med Genet. 2009 Sep 15;10:91
references.pmid: 19754948
references.citation: J Clin Lab Anal. 2003;17(6):259-63
references.pmid: 14614750
references.citation: Br J Ophthalmol. 2006 Mar;90(3):262-7
references.pmid: 16488940
references.citation: Ophthalmol Clin North Am. 2003 Dec;16(4):639-45
references.pmid: 14741004
references.citation: Mol Vis. 2006 Aug 29;12:1016-21
references.pmid: 16971893
references.citation: Annu Rev Pharmacol Toxicol. 2008;48:333-58
references.pmid: 17914928
references.citation: Prog Brain Res. 2008;173:511-9
references.pmid: 18929131
references.citation: Arch Ophthalmol. 2010 Mar;128(3):276-87
references.pmid: 20212196
references.citation: Hum Mol Genet. 2009 Oct 15;18(20):3969-77
references.pmid: 19656777
references.citation: Hum Mol Genet. 2000 Apr 12;9(7):1109-17
references.pmid: 10767336
references.citation: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5315-21
references.pmid: 17122119
references.citation: Invest Ophthalmol Vis Sci. 2010 Aug;51(8):4110-6
references.pmid: 20357201
references.citation: Am J Ophthalmol. 1998 Jul;126(1):17-28
references.pmid: 9683145
references.citation: Methods Enzymol. 2008;438:11-24
references.pmid: 18413238
references.citation: Invest Ophthalmol Vis Sci. 2010 Jan;51(1):72-8
references.pmid: 19696176
references.citation: Clin Exp Ophthalmol. 2009 Mar;37(2):201-7
references.pmid: 19723129
references.citation: Ophthalmology. 1996 May;103(5):808-14
references.pmid: 8637692
references.citation: Invest Ophthalmol Vis Sci. 2010 Feb;51(2):971-9
references.pmid: 19815736
references.citation: Hum Mol Genet. 2005 Mar 15;14(6):725-33
references.pmid: 15677485
references.citation: Nat Genet. 2002 Jan;30(1):81-5
references.pmid: 11743578
references.citation: Exp Eye Res. 2009 Apr;88(4):747-51
references.pmid: 19061887
references.citation: Hum Genet. 2010 Jan;127(1):33-44
references.pmid: 19714363
references.citation: Science. 2002 Feb 8;295(5557):1077-9
references.pmid: 11834836
references.citation: Nat Genet. 2004 Feb;36(2):178-82
references.pmid: 14745449
references.citation: Mol Cell Biol. 2001 Nov;21(22):7707-13
references.pmid: 11604506
references.citation: Arch Ophthalmol. 1997 Feb;115(2):182-5
references.pmid: 9046252
references.citation: Hum Mol Genet. 2010 Jul 1;19(13):2606-15
references.pmid: 20388642
references.citation: Am J Pathol. 2010 Jun;176(6):2880-90
references.pmid: 20382707
references.citation: Am J Hum Genet. 1998 Nov;63(5):1411-8
references.pmid: 9792868
references.citation: Invest Ophthalmol Vis Sci. 2010 Apr;51(4):2051-9
references.pmid: 19933193
references.citation: Clin Exp Ophthalmol. 2008 Dec;36(9):868-82
references.pmid: 19278484
references.citation: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3976-80
references.pmid: 18450598
references.citation: Exp Eye Res. 2009 Apr;88(4):808-15
references.pmid: 19217904
references.citation: J Biol Chem. 2005 Dec 30;280(52):42848-55
references.pmid: 16251195
references.citation: Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4244-53
references.pmid: 19357352
references.citation: Hum Mol Genet. 2000 Apr 12;9(7):1021-32
references.pmid: 10767326
references.citation: Invest Ophthalmol Vis Sci. 2005 Aug;46(8):2816-22
references.pmid: 16043855
references.citation: Mol Vis. 2010 Jan 11;16:18-25
references.pmid: 20069064
references.citation: J Med Genet. 2010 Feb;47(2):120-5
references.pmid: 19581274
references.citation: Proc Natl Acad Sci U S A. 2005 Jul 5;102(27):9553-8
references.pmid: 15976030
references.citation: Am J Hum Genet. 2009 Oct;85(4):447-56
references.pmid: 19765683
references.citation: Ophthalmology. 2009 Apr;116(4):710-6, 716.e1-82
references.pmid: 19344823
references.citation: Exp Eye Res. 2008 Apr;86(4):543-61
references.pmid: 18313051
references.citation: Ophthalmology. 1995 Dec;102(12):1782-9
references.pmid: 9098278
references.citation: J Glaucoma. 2006 Oct;15(5):358-63
references.pmid: 16988596
references.citation: Exp Eye Res. 2009 Apr;88(4):648-55
references.pmid: 19239914
references.citation: Am J Hum Genet. 1998 Feb;62(2):325-33
references.pmid: 9463332
references.citation: Invest Ophthalmol Vis Sci. 2009 May;50(5):2194-200
references.pmid: 19060281
references.citation: Vis Neurosci. 2008 Jul-Aug;25(4):563-74
references.pmid: 18764959
references.citation: Genomics. 1997 May 1;41(3):360-9
references.pmid: 9169133
references.citation: Int J Dev Biol. 2004;48(8-9):1015-29
references.pmid: 15558492
references.citation: Drug Discov Today. 2010 Apr;15(7-8):287-99
references.pmid: 20197108
references.citation: Hum Mol Genet. 1999 May;8(5):899-905
references.pmid: 10196380
references.citation: Clin Biochem. 2006 Mar;39(3):249-58
references.pmid: 16332362
references.citation: Invest Ophthalmol Vis Sci. 2007 Aug;48(8):3669-76
references.pmid: 17652737
references.citation: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1486-90
references.pmid: 16565383
references.citation: Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4087-90
references.pmid: 19420341