title: Development of diagnostic and treatment strategies for glaucoma through understanding and modification of scleral and lamina cribrosa connective tissue.
abstract: Considerable evidence indicates that the state of ocular connective tissues and their response in glaucomatous disease affect the degree of glaucoma damage. Both experimental and clinical data suggest that improved diagnostic and prognostic information can be derived from the assessment of the mechanical responsiveness of the sclera and lamina cribrosa to intraocular pressure (IOP). Controlled mutagenesis of the sclera has produced a mouse strain that is relatively resistant to increased IOP. Alteration of the baseline scleral state can be accomplished through either increased cross-linking of fibrillar components or their reduction. The sclera is a dynamic structure, altering its structure and behavior in response to IOP change. The biochemical pathways that control these responses are fertile areas for new glaucoma treatments.
authors.affiliation: Glaucoma Center of Excellence, Wilmer Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Harry A
authors.initials: HA
authors.lastname: Quigley
authors.forename: Frances E
authors.initials: FE
authors.lastname: Cone
mesh_terms: D000818:Animals; D003238:Connective Tissue / Q000473:pathology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005901:Glaucoma / Q000175:diagnosis* / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D007429:Intraocular Pressure; D012590:Sclera / Q000473:pathology* / Q000503:physiopathology; D013312:Stress, Physiological
references.citation: Curr Eye Res. 1991 Sep;10(9):877-88
references.pmid: 1790718
references.citation: Arch Ophthalmol. 1981 Apr;99(4):635-49
references.pmid: 6164357
references.citation: J Mol Biol. 1988 Sep 20;203(2):495-505
references.pmid: 3143838
references.citation: Invest Ophthalmol Vis Sci. 2011 Sep 09;52(10):7109-21
references.pmid: 21715355
references.citation: Am J Ophthalmol. 1990 Feb 15;109(2):180-8
references.pmid: 2405683
references.citation: Adv Drug Deliv Rev. 2005 Jan 2;57(1):63-78
references.pmid: 15518921
references.citation: Graefes Arch Clin Exp Ophthalmol. 1994 May;232(5):257-61
references.pmid: 8045433
references.citation: Am J Ophthalmol. 1983 May;95(5):673-91
references.pmid: 6846459
references.citation: Invest Ophthalmol Vis Sci. 1992 Sep;33(10):2891-903
references.pmid: 1526740
references.citation: Invest Ophthalmol Vis Sci. 2011 Aug 17;52(9):6511-21
references.pmid: 21746802
references.citation: Br J Ophthalmol. 1991 Sep;75(9):552-7
references.pmid: 1911659
references.citation: Arch Ophthalmol. 1981 Jan;99(1):137-43
references.pmid: 7458737
references.citation: Connect Tissue Res. 2009;50(4):211-22
references.pmid: 19637057
references.citation: Trans Am Ophthalmol Soc. 2001;99:319-43
references.pmid: 11797317
references.citation: Surv Ophthalmol. 2007 Nov;52 Suppl 2:S144-54
references.pmid: 17998040
references.citation: Invest Ophthalmol Vis Sci. 2006 May;47(5):1794-802
references.pmid: 16638983
references.citation: Invest Ophthalmol. 1974 Jun;13(6):455-7
references.pmid: 4208801
references.citation: Optom Vis Sci. 2009 Jan;86(1):E23-30
references.pmid: 19104466
references.citation: Invest Ophthalmol Vis Sci. 2004 Jun;45(6):1841-5
references.pmid: 15161848
references.citation: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3209-15
references.pmid: 17591890
references.citation: Am J Ophthalmol. 2003 May;135(5):620-7
references.pmid: 12719068
references.citation: Proc Natl Acad Sci U S A. 2005 Aug 23;102(34):12242-7
references.pmid: 16103353
references.citation: Mol Vis. 2008 Jan 29;14:150-60
references.pmid: 18334929
references.citation: J Clin Invest. 2012 Apr;122(4):1246-61
references.pmid: 22426214
references.citation: J Biomech. 1983;16(1):1-12
references.pmid: 6833305
references.citation: Invest Ophthalmol Vis Sci. 2008 May;49(5):1932-9
references.pmid: 18436825
references.citation: Exp Eye Res. 1997 Jan;64(1):85-96
references.pmid: 9093024
references.citation: Mol Vis. 2011;17:1745-58
references.pmid: 21738403
references.citation: Invest Ophthalmol Vis Sci. 2011 Mar 30;52(3):1896-907
references.pmid: 20881292
references.citation: Eur J Neurosci. 2004 Jan;19(2):265-72
references.pmid: 14725620
references.citation: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4046-50
references.pmid: 18487379
references.citation: Mol Vis. 2009;15:76-88
references.pmid: 19145252
references.citation: Graefes Arch Clin Exp Ophthalmol. 2005 Jun;243(6):513-8
references.pmid: 15756577
references.citation: Invest Ophthalmol Vis Sci. 2011 Feb 11;52(2):821-9
references.pmid: 21051726
references.citation: J Glaucoma. 2007 Jun-Jul;16(4):406-18
references.pmid: 17571004
references.citation: Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4232-6
references.pmid: 18539943
references.citation: Exp Eye Res. 2006 Feb;82(2):185-200
references.pmid: 16202407
references.citation: Invest Ophthalmol Vis Sci. 2013 Mar 11;54(3):1767-80
references.pmid: 23404116
references.citation: J Biomech. 2007;40(11):2367-76
references.pmid: 17240381
references.citation: Invest Ophthalmol Vis Sci. 2011 Aug 11;52(9):6363-9
references.pmid: 21724915
references.citation: J Neurosci. 2006 Nov 15;26(46):11903-14
references.pmid: 17108164
references.citation: Arch Ophthalmol. 1990 Jul;108(7):1020-4
references.pmid: 2369339
references.citation: J Glaucoma. 2002 Jun;11(3):221-5
references.pmid: 12140399
references.citation: Exp Eye Res. 1972 Jul;14(1):29-39
references.pmid: 5039845
references.citation: Invest Ophthalmol Vis Sci. 2011 Jul 29;52(8):5656-69
references.pmid: 21519033
references.citation: Invest Ophthalmol Vis Sci. 2003 Oct;44(10):4357-65
references.pmid: 14507880
references.citation: J Neurosci. 2006 Dec 6;26(49):12633-41
references.pmid: 17151265
references.citation: Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5226-37
references.pmid: 19494203
references.citation: Mol Vis. 2012;18:1093-106
references.pmid: 22701298
references.citation: Invest Ophthalmol Vis Sci. 1995 Aug;36(9):1893-903
references.pmid: 7543465
references.citation: Exp Eye Res. 2010 Dec;91(6):866-75
references.pmid: 20868685
references.citation: Invest Ophthalmol Vis Sci. 2009 Apr;50(4):1606-12
references.pmid: 19060268
references.citation: Nat Genet. 2003 Mar;33(3):407-11
references.pmid: 12598898
references.citation: J Clin Invest. 2004 Dec;114(11):1586-92
references.pmid: 15546004
references.citation: J Comp Neurol. 2009 Sep 1;516(1):1-19
references.pmid: 19562764
references.citation: Biochim Biophys Acta. 1992 Mar 20;1138(3):222-8
references.pmid: 1547284
references.citation: J Cataract Refract Surg. 2008 Apr;34(4):651-6
references.pmid: 18361989
references.citation: Invest Ophthalmol Vis Sci. 2011 Jul 15;52(8):5240-50
references.pmid: 21546528
references.citation: Am J Ophthalmol. 1998 Feb;125(2):237-41
references.pmid: 9467451
references.citation: Science. 2007 Sep 7;317(5843):1397-400
references.pmid: 17690259
references.citation: Matrix Biol. 2010 Apr;29(3):228-36
references.pmid: 20026402
references.citation: Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1286-90
references.pmid: 15790892
references.citation: Exp Eye Res. 2012 Jun;99:27-35
references.pmid: 22554836
references.citation: Exp Eye Res. 2010 Sep;91(3):415-24
references.pmid: 20599961
references.citation: Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4189-99
references.pmid: 16249498
references.citation: Eye (Lond). 2009 Mar;23(3):606-11
references.pmid: 18309334
references.citation: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3177-87
references.pmid: 16123417
references.citation: Am J Pathol. 2012 Jun;180(6):2386-403
references.pmid: 22542845
references.citation: Invest Ophthalmol Vis Sci. 1998 May;39(6):951-62
references.pmid: 9579474
references.citation: Ophthalmology. 2004 Sep;111(9):1627-35
references.pmid: 15350314
references.citation: Br J Ophthalmol. 1999 Feb;83(2):209-18
references.pmid: 10396201
references.citation: Invest Ophthalmol Vis Sci. 1995 Apr;36(5):774-86
references.pmid: 7706025
references.citation: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3195-208
references.pmid: 17591889
references.citation: Science. 2011 Apr 15;332(6027):361-5
references.pmid: 21493863
references.citation: Br J Ophthalmol. 2006 Mar;90(3):383-8
references.pmid: 16488967
references.citation: Prog Retin Eye Res. 2005 Jan;24(1):39-73
references.pmid: 15555526
references.citation: J Biol Chem. 2004 Apr 30;279(18):18121-6
references.pmid: 14752095
references.citation: Invest Ophthalmol Vis Sci. 2010 Jan;51(1):207-16
references.pmid: 19850836
references.citation: Arch Ophthalmol. 1997 Aug;115(8):1031-5
references.pmid: 9258226
references.citation: Ophthalmology. 1979 Oct;86(10):1803-30
references.pmid: 553256
references.citation: Invest Ophthalmol Vis Sci. 2012 Aug 31;53(9):5956-66
references.pmid: 22859742
references.citation: Curr Opin Pharmacol. 2013 Feb;13(1):83-9
references.pmid: 22999652
references.citation: Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1001-12
references.pmid: 19244206
references.citation: Invest Ophthalmol Vis Sci. 2005 Feb;46(2):540-6
references.pmid: 15671280
references.citation: Arch Ophthalmol. 2002 Jun;120(6):701-13; discussion 829-30
references.pmid: 12049574
references.citation: Exp Eye Res. 2012 Jul;100:65-72
references.pmid: 22575566
references.citation: Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1407-11
references.pmid: 12657572
references.citation: Invest Ophthalmol Vis Sci. 2000 Jul;41(8):2028-34
references.pmid: 10892839
references.citation: Invest Ophthalmol Vis Sci. 1998 Mar;39(3):526-31
references.pmid: 9501862
references.citation: Science. 2006 Apr 7;312(5770):117-21
references.pmid: 16601194
references.citation: Invest Ophthalmol Vis Sci. 1997 Nov;38(12):2435-46
references.pmid: 9375560
references.citation: Invest Ophthalmol Vis Sci. 2012 Aug 07;53(9):5258-70
references.pmid: 22786908
references.citation: Arch Ophthalmol. 2002 Oct;120(10):1268-79
references.pmid: 12365904
references.citation: Mol Ther. 2002 Jun;5(6):780-7
references.pmid: 12027563
references.citation: Invest Ophthalmol Vis Sci. 2012 Apr 02;53(4):1714-28
references.pmid: 22395883
references.citation: Biomech Model Mechanobiol. 2013 Oct;12(5):941-63
references.pmid: 23188256
references.citation: Invest Ophthalmol Vis Sci. 2011 Apr 01;52(5):2679-88
references.pmid: 21282566
references.citation: Am J Ophthalmol. 2006 May;141(5):868-75
references.pmid: 16527231
references.citation: Invest Ophthalmol Vis Sci. 2007 Jul;48(7):3161-77
references.pmid: 17591886
references.citation: Invest Ophthalmol Vis Sci. 2011 Jan 21;52(1):434-41
references.pmid: 20811062