title: Therapeutic targets in age-related macular disease.
abstract: Age-related macular disease (AMD) accounts for more than 50% of blind registration in Western society. Patients with AMD are classified as having early disease, in which visual function is well preserved, or late disease, in which central vision is lost. Until recently, there was no therapy available by which the course of the disorder could be modified. Now, the most common form of late-stage AMD - choroidal neovascularization - responds to treatment with anti-VEGF therapies; although visual loss is modified in a portion of these cases, no therapeutic approach exists that alters the evolution from early to late disease. However, as discussed in this Review, research over the last few years has demonstrated several features of AMD that are likely to be amenable to treatment. Potential targets for treatment are described, and possible therapeutic approaches are discussed.
authors.affiliation: Institute of Ophthalmology, University College London, and Moorfields Eye Hospital, London, UK. Alan.bird@ucl.ac.uk
authors.forename: Alan C
authors.initials: AC
authors.lastname: Bird
mesh_terms: D000375:Aging; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D001766:Blindness / Q000188:drug therapy; D020256:Choroidal Neovascularization / Q000188:drug therapy*; D004195:Disease Models, Animal; D005123:Eye / Q000033:anatomy & histology / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D008268:Macular Degeneration / Q000145:classification / Q000188:drug therapy* / Q000628:therapy; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D012106:Research / Q000639:trends; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000627:therapeutic use
chemical_list: D020533:Angiogenesis Inhibitors; D042461:Vascular Endothelial Growth Factor A
references.citation: Ophthalmology. 1995 Oct;102(10):1450-60
references.pmid: 9097791
references.citation: Br J Ophthalmol. 1996 Jan;80(1):9-14
references.pmid: 8664242
references.citation: Invest Ophthalmol Vis Sci. 2008 Jul;49(7):3095-9
references.pmid: 18378583
references.citation: Invest Ophthalmol Vis Sci. 2005 Jul;46(7):2576-86
references.pmid: 15980251
references.citation: Graefes Arch Clin Exp Ophthalmol. 1991;229(5):406-10
references.pmid: 1937071
references.citation: Trans Ophthalmol Soc U K. 1983;103 ( Pt 4):416-21
references.pmid: 6589859
references.citation: Invest Ophthalmol Vis Sci. 1992 Feb;33(2):334-40
references.pmid: 1740363
references.citation: Nat Genet. 2008 Jul;40(7):892-6
references.pmid: 18511946
references.citation: Science. 2005 Apr 15;308(5720):419-21
references.pmid: 15761120
references.citation: Invest Ophthalmol Vis Sci. 1997 Mar;38(3):762-7
references.pmid: 9071230
references.citation: Proc Natl Acad Sci U S A. 2007 Oct 16;104(42):16651-6
references.pmid: 17921253
references.citation: Curr Eye Res. 1999 Mar;18(3):203-13
references.pmid: 10342375
references.citation: Ophthalmology. 1993 Jan;100(1):47-51
references.pmid: 8433826
references.citation: Science. 2005 Apr 15;308(5720):385-9
references.pmid: 15761122
references.citation: Ophthalmology. 1992 Oct;99(10):1548-53
references.pmid: 1454321
references.citation: Ophthalmology. 1985 May;92(5):628-35
references.pmid: 2409505
references.citation: Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32
references.pmid: 15870199
references.citation: Prog Retin Eye Res. 2010 Mar;29(2):95-112
references.pmid: 19961953
references.citation: Jpn J Ophthalmol. 1991;35(3):268-72
references.pmid: 1770666
references.citation: J Clin Invest. 2005 Oct;115(10):2793-800
references.pmid: 16167083
references.citation: Br J Ophthalmol. 1988 Dec;72(12):918-20
references.pmid: 3228547
references.citation: Albrecht Von Graefes Arch Ophthalmol. 1948;148(3-4):287-317
references.pmid: 18868814
references.citation: Trans Am Ophthalmol Soc. 1977;75:180-254
references.pmid: 613523
references.citation: Invest Ophthalmol Vis Sci. 1994 May;35(6):2857-64
references.pmid: 8188481
references.citation: Am J Ophthalmol. 2002 Mar;133(3):341-9
references.pmid: 11860971
references.citation: Ann Med. 2006;38(8):592-604
references.pmid: 17438673
references.citation: Invest Ophthalmol Vis Sci. 1990 May;31(5):899-908
references.pmid: 1692312
references.citation: Br J Ophthalmol. 1993 Sep;77(9):549-54
references.pmid: 8218049
references.citation: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7154-9
references.pmid: 10852960
references.citation: Br J Ophthalmol. 1995 May;79(5):407-12
references.pmid: 7612549
references.citation: Am J Ophthalmol. 1988 Mar 15;105(3):285-90
references.pmid: 2449819
references.citation: Arch Ophthalmol. 1995 Jun;113(6):728-35
references.pmid: 7786213
references.citation: N Engl J Med. 2007 Aug 9;357(6):553-61
references.pmid: 17634448
references.citation: Hum Mol Genet. 2005 Nov 1;14(21):3227-36
references.pmid: 16174643
references.citation: Invest Ophthalmol Vis Sci. 2006 Aug;47(8):3612-24
references.pmid: 16877436
references.citation: Jpn J Ophthalmol. 1991;35(1):87-95
references.pmid: 1716707
references.citation: Am J Ophthalmol. 2008 Oct;146(4):496-500
references.pmid: 18639219
references.citation: Exp Eye Res. 2009 Feb;88(2):195-203
references.pmid: 18588875
references.citation: N Engl J Med. 2006 Oct 5;355(14):1474-85
references.pmid: 17021323
references.citation: Arch Ophthalmol. 1994 Mar;112(3):402-6
references.pmid: 8129668
references.citation: Acta Ophthalmol Scand. 2006 Oct;84(5):636-41
references.pmid: 16965494
references.citation: Am J Pathol. 1999 Aug;155(2):421-8
references.pmid: 10433935
references.citation: Am J Ophthalmol. 1990 Feb 15;109(2):211-7
references.pmid: 2301534
references.citation: Invest Ophthalmol Vis Sci. 2002 Jul;43(7):2088-96
references.pmid: 12091401
references.citation: J Mol Biol. 2008 Dec 31;384(5):1341-52
references.pmid: 18976665
references.citation: Neuroscience. 2009 Aug 18;162(2):375-82
references.pmid: 19422885
references.citation: Exp Eye Res. 2007 Apr;84(4):772-80
references.pmid: 17313944
references.citation: Invest Ophthalmol Vis Sci. 1995 Mar;36(3):718-29
references.pmid: 7890502
references.citation: Prog Retin Eye Res. 2003 Jan;22(1):1-29
references.pmid: 12597922
references.citation: Ophthalmology. 2007 Jun;114(6):1157-63
references.pmid: 17337063
references.citation: Arctic Med Res. 1987 Oct;46(2):64-70
references.pmid: 3426774
references.citation: Invest Ophthalmol Vis Sci. 2001 Apr;42(5):1051-6
references.pmid: 11274085
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 26;104(26):11026-31
references.pmid: 17578916
references.citation: Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1275-81
references.pmid: 20185837
references.citation: Ophthalmology. 1989 Dec;96(12):1769-77
references.pmid: 2482957
references.citation: Trans Am Acad Ophthalmol Otolaryngol. 1965 Jul-Aug;69:683-90
references.pmid: 14345773
references.citation: Invest Ophthalmol Vis Sci. 2000 Dec;41(13):4305-12
references.pmid: 11095631
references.citation: Graefes Arch Clin Exp Ophthalmol. 2009 May;247(5):651-9
references.pmid: 19214553
references.citation: Eur J Hum Genet. 2009 Sep;17(9):1190-9
references.pmid: 19259132
references.citation: J Alzheimers Dis. 2009;16(3):471-83
references.pmid: 19276540
references.citation: Retina. 2001;21(5):416-34
references.pmid: 11642370
references.citation: Prog Retin Eye Res. 2001 Nov;20(6):705-32
references.pmid: 11587915
references.citation: Exp Eye Res. 2004 Feb;78(2):243-56
references.pmid: 14729357
references.citation: Invest Ophthalmol Vis Sci. 2009 Oct;50(10):4982-91
references.pmid: 19357355
references.citation: Proc Natl Acad Sci U S A. 1995 Jan 31;92(3):905-9
references.pmid: 7846076
references.citation: Ophthalmology. 1991 Jun;98(6):953-6
references.pmid: 1866150
references.citation: J Lipid Res. 1991 Dec;32(12):2009-17
references.pmid: 1840067
references.citation: Invest Ophthalmol Vis Sci. 1996 Aug;37(9):1929-34
references.pmid: 8759365
references.citation: Invest Ophthalmol Vis Sci. 1996 Jun;37(7):1236-49
references.pmid: 8641827
references.citation: Invest Ophthalmol Vis Sci. 2002 May;43(5):1574-80
references.pmid: 11980876
references.citation: Arch Ophthalmol. 1964 Jun;71:842-50
references.pmid: 14133872
references.citation: Invest Ophthalmol Vis Sci. 1999 Feb;40(2):443-9
references.pmid: 9950604
references.citation: Invest Ophthalmol Vis Sci. 1999 Mar;40(3):737-43
references.pmid: 10067978
references.citation: Invest Ophthalmol Vis Sci. 1984 Oct;25(10):1135-45
references.pmid: 6480292
references.citation: Surv Ophthalmol. 2000 Sep-Oct;45(2):115-34
references.pmid: 11033038
references.citation: Med Sci Monit. 2010 Jan;16(1):BR17-23
references.pmid: 20037481
references.citation: Br J Ophthalmol. 1976 May;60(5):324-41
references.pmid: 952802
references.citation: Zhonghua Yi Xue Za Zhi (Taipei). 1995 Dec;56(6):411-7
references.pmid: 8851483
references.citation: Invest Ophthalmol Vis Sci. 2009 Mar;50(3):1392-9
references.pmid: 19029031
references.citation: Science. 2005 Apr 15;308(5720):421-4
references.pmid: 15761121
references.citation: Nippon Ganka Gakkai Zasshi. 1988 Oct;92(10):1629-36
references.pmid: 2463748
references.citation: Ann Acad Med Singap. 2002 May;31(3):399-404
references.pmid: 12061304
references.citation: Exp Eye Res. 2006 Jan;82(1):99-110
references.pmid: 16019000
references.citation: Invest Ophthalmol Vis Sci. 2010 Mar;51(3):1304-10
references.pmid: 19892876
references.citation: Trans Am Acad Ophthalmol Otolaryngol. 1972 Jan-Feb;76(1):64-80
references.pmid: 5024602
references.citation: J Formos Med Assoc. 1993 Sep;92(9):823-8
references.pmid: 7507372
references.citation: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11830-5
references.pmid: 12189211
references.citation: Ophthalmology. 1992 Jun;99(6):933-43
references.pmid: 1630784
references.citation: Eye (Lond). 1989;3 ( Pt 5):588-96
references.pmid: 2630336
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 3;106(44):18751-6
references.pmid: 19841260
references.citation: Exp Eye Res. 1992 Feb;54(2):239-46
references.pmid: 1559552
references.citation: Ophthalmology. 1995 Feb;102(2):205-10
references.pmid: 7862408
references.citation: Invest Ophthalmol Vis Sci. 2004 Feb;45(2):574-83
references.pmid: 14744901
references.citation: Arch Ophthalmol. 2003 Mar;121(3):379-85
references.pmid: 12617709
references.citation: Am J Ophthalmol. 2000 Nov;130(5):658-63
references.pmid: 11078846
references.citation: Ophthalmology. 1989 Dec;96(12):1763-8
references.pmid: 2622621
references.citation: Invest Ophthalmol Vis Sci. 2008 Sep;49(9):4137-44
references.pmid: 18487363
references.citation: Am J Ophthalmol. 2007 Dec;144(6):850-857
references.pmid: 17949673
references.citation: FASEB J. 1999 Mar;13(3):477-84
references.pmid: 10064614
references.citation: Graefes Arch Clin Exp Ophthalmol. 2002 Dec;240(12):983-8
references.pmid: 12483320
references.citation: Am J Pathol. 1994 Sep;145(3):574-84
references.pmid: 7521577
references.citation: Mol Vis. 2006 Dec 22;12:1649-59
references.pmid: 17200665
references.citation: Br J Ophthalmol. 1978 Aug;62(8):547-50
references.pmid: 687553
references.citation: Invest Ophthalmol Vis Sci. 1995 Jun;36(7):1290-7
references.pmid: 7775106
references.citation: Ophthalmology. 1990 Feb;97(2):171-8
references.pmid: 1691475
references.citation: Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4742-7
references.pmid: 12671074
references.citation: Exp Eye Res. 2007 Dec;85(6):762-71
references.pmid: 17915218
references.citation: J Neurochem. 1991 Nov;57(5):1690-9
references.pmid: 1833510
references.citation: Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5304-9
references.pmid: 19407013
references.citation: BMJ. 2003 Feb 1;326(7383):255-6
references.pmid: 12560276
references.citation: Ophthalmology. 2007 Feb;114(2):246-52
references.pmid: 17270674
references.citation: Arctic Med Res. 1987;46(1):13-7
references.pmid: 3675777
references.citation: Trans Ophthalmol Soc U K. 1986;105 ( Pt 6):674-82
references.pmid: 3310342