KEGG   DISEASE: Age-related macular degeneration
Entry
H00821                      Disease                                
Name
Age-related macular degeneration
Description
Macular degeneration is the physical breakdown of the central portion of the retina called the macula. Age-related macular degeneration (AMD/ARMD) is the leading cause of blindness. AMD is a complex disease caused by the combination of genetic predisposition and environmental factors. Using genome linkage scan and association studies, multiple potentially causative genes have been identified. In AMD, there are two phenotypes, atrophic/ dry and neovascular/ wet. The former is characterized by the geographic atrophy due to death of retinal pigment epithelium, and the latter is usually characterized by the abnormal growth of new blood vessels under the macula, which causes severe loss of vision. While wet AMD can be treated by the inhibition of vascular endothelial growth factor or photodynamic therapy, so far there are no available treatments for dry AMD.
Category
Nervous system disease
Brite
Human diseases [BR:br08402]
 Nervous system diseases
  Eye disease
   H00821  Age-related macular degeneration
Human diseases in ICD-11 classification [BR:br08403]
 09 Diseases of the visual system
  Disorders of the eyeball posterior segment
   Disorders of the retina
    9B75  Macular disorders
     H00821  Age-related macular degeneration
Related
pathway
hsa04610  Complement and coagulation cascades
Network
nt06513  Complement cascade
Gene
(ARMD1) HMCN1 [HSA:83872] [KO:K17341]
(ARMD1) CFHR1 [HSA:3078] [KO:K23815]
(ARMD1) CFHR3 [HSA:10878] [KO:K23815]
(ARMD2) ABCA4 [HSA:24] [KO:K05644]
(ARMD3) FBLN5 [HSA:10516] [KO:K17340]
(ARMD4) CFH [HSA:3075] [KO:K04004]
(ARMD5) ERCC6 [HSA:2074] [KO:K10841]
(ARMD6) RAX2 [HSA:84839] [KO:K09333]
(ARMD7) HTRA1 [HSA:5654] [KO:K08784]
(ARMD8) ARMS2 [HSA:387715] [KO:K25179]
(ARMD9) C3 [HSA:718] [KO:K03990]
(ARMD10) TLR4 [HSA:7099] [KO:K10160]
(ARMD11) CST3 [HSA:1471] [KO:K13899]
(ARMD12) CX3CR1 [HSA:1524] [KO:K04192]
(ARMD13) CFI [HSA:3426] [KO:K01333]
(ARMD14) C2 [HSA:717] [KO:K01332]
(ARMD14) CFB [HSA:629] [KO:K01335]
(ARMD15) C9 [HSA:735] [KO:K04000]
Drug
Aflibercept [DR:D09574]
Verteporfin [DR:D01162]
Ranibizumab [DR:D05697]
Brolucizumab [DR:D11083]
Faricimab [DR:D11516]
Comment
A haplotype carrying deletion of the complement factor H-related genes CFHR1 and CFHR3 is also associated with reduced risk of ARMD.
Other DBs
ICD-11: 9B75.0
ICD-10: H35.3
MeSH: D008268
OMIM: 603075 153800 608895 610698 613761 613757 610149 613778 611378 611488 611953 613784 615439 615489 615591
Reference
  Authors
Montezuma SR, Sobrin L, Seddon JM
  Title
Review of genetics in age related macular degeneration.
  Journal
Semin Ophthalmol 22:229-40 (2007)
DOI:10.1080/08820530701745140
Reference
  Authors
Virgili G, Bini A
  Title
Laser photocoagulation for neovascular age-related macular degeneration.
  Journal
Cochrane Database Syst Rev CD004763 (2007)
DOI:10.1002/14651858.CD004763.pub2
Reference
PMID:14570714 (HMCN1)
  Authors
Schultz DW, Klein ML, Humpert AJ, Luzier CW, Persun V, Schain M, Mahan A, Runckel C, Cassera M, Vittal V, Doyle TM, Martin TM, Weleber RG, Francis PJ, Acott TS
  Title
Analysis of the ARMD1 locus: evidence that a mutation in HEMICENTIN-1 is associated with age-related macular degeneration in a large family.
  Journal
Hum Mol Genet 12:3315-23 (2003)
DOI:10.1093/hmg/ddg348
Reference
PMID:16998489 (CFHR1 CFHR3, reduced risk)
  Authors
Hughes AE, Orr N, Esfandiary H, Diaz-Torres M, Goodship T, Chakravarthy U
  Title
A common CFH haplotype, with deletion of CFHR1 and CFHR3, is associated with lower risk of age-related macular degeneration.
  Journal
Nat Genet 38:1173-7 (2006)
DOI:10.1038/ng1890
Reference
PMID:9295268 (ABCA4)
  Authors
Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, Peiffer A, Zabriskie NA, Li Y, Hutchinson A, Dean M, Lupski JR, Leppert M
  Title
Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration.
  Journal
Science 277:1805-7 (1997)
DOI:10.1126/science.277.5333.1805
Reference
PMID:15269314 (FBLN5)
  Authors
Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery AJ, Moore PA, Eastman CG, Casavant TL, Sheffield VC
  Title
Missense variations in the fibulin 5 gene and age-related macular degeneration.
  Journal
N Engl J Med 351:346-53 (2004)
DOI:10.1056/NEJMoa040833
Reference
PMID:15761122 (CFH)
  Authors
Klein RJ, Zeiss C, Chew EY, Tsai JY, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J
  Title
Complement factor H polymorphism in age-related macular degeneration.
  Journal
Science 308:385-9 (2005)
DOI:10.1126/science.1109557
Reference
PMID:16754848 (ERCC6)
  Authors
Tuo J, Ning B, Bojanowski CM, Lin ZN, Ross RJ, Reed GF, Shen D, Jiao X, Zhou M, Chew EY, Kadlubar FF, Chan CC
  Title
Synergic effect of polymorphisms in ERCC6 5' flanking region and complement factor H on age-related macular degeneration predisposition.
  Journal
Proc Natl Acad Sci U S A 103:9256-61 (2006)
DOI:10.1073/pnas.0603485103
Reference
PMID:15028672 (RAX2)
  Authors
Wang QL, Chen S, Esumi N, Swain PK, Haines HS, Peng G, Melia BM, McIntosh I, Heckenlively JR, Jacobson SG, Stone EM, Swaroop A, Zack DJ
  Title
QRX, a novel homeobox gene, modulates photoreceptor gene expression.
  Journal
Hum Mol Genet 13:1025-40 (2004)
DOI:10.1093/hmg/ddh117
Reference
PMID:17053108 (HTRA1)
  Authors
Dewan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS, Snyder M, Barnstable C, Pang CP, Hoh J
  Title
HTRA1 promoter polymorphism in wet age-related macular degeneration.
  Journal
Science 314:989-92 (2006)
DOI:10.1126/science.1133807
Reference
PMID:16174643 (ARMS2)
  Authors
Rivera A, Fisher SA, Fritsche LG, Keilhauer CN, Lichtner P, Meitinger T, Weber BH
  Title
Hypothetical LOC387715 is a second major susceptibility gene for age-related macular degeneration, contributing independently of complement factor H to disease risk.
  Journal
Hum Mol Genet 14:3227-36 (2005)
DOI:10.1093/hmg/ddi353
Reference
PMID:17634448 (C3)
  Authors
Yates JR, Sepp T, Matharu BK, Khan JC, Thurlby DA, Shahid H, Clayton DG, Hayward C, Morgan J, Wright AF, Armbrecht AM, Dhillon B, Deary IJ, Redmond E, Bird AC, Moore AT
  Title
Complement C3 variant and the risk of age-related macular degeneration.
  Journal
N Engl J Med 357:553-61 (2007)
DOI:10.1056/NEJMoa072618
Reference
PMID:15829498 (TLR4)
  Authors
Zareparsi S, Buraczynska M, Branham KE, Shah S, Eng D, Li M, Pawar H, Yashar BM, Moroi SE, Lichter PR, Petty HR, Richards JE, Abecasis GR, Elner VM, Swaroop A
  Title
Toll-like receptor 4 variant D299G is associated with susceptibility to age-related macular degeneration.
  Journal
Hum Mol Genet 14:1449-55 (2005)
DOI:10.1093/hmg/ddi154
Reference
PMID:11815350 (CST3)
  Authors
Zurdel J, Finckh U, Menzer G, Nitsch RM, Richard G
  Title
CST3 genotype associated with exudative age related macular degeneration.
  Journal
Br J Ophthalmol 86:214-9 (2002)
DOI:10.1136/bjo.86.2.214
Reference
PMID:15208270 (CX3CR1)
  Authors
Tuo J, Smith BC, Bojanowski CM, Meleth AD, Gery I, Csaky KG, Chew EY, Chan CC
  Title
The involvement of sequence variation and expression of CX3CR1 in the pathogenesis of age-related macular degeneration.
  Journal
FASEB J 18:1297-9 (2004)
DOI:10.1096/fj.04-1862fje
Reference
PMID:23685748 (CFI)
  Authors
van de Ven JP, Nilsson SC, Tan PL, Buitendijk GH, Ristau T, Mohlin FC, Nabuurs SB, Schoenmaker-Koller FE, Smailhodzic D, Campochiaro PA, Zack DJ, Duvvari MR, Bakker B, Paun CC, Boon CJ, Uitterlinden AG, Liakopoulos S, Klevering BJ, Fauser S, Daha MR, Katsanis N, Klaver CC, Blom AM, Hoyng CB, den Hollander AI
  Title
A functional variant in the CFI gene confers a high risk of age-related macular degeneration.
  Journal
Nat Genet 45:813-7 (2013)
DOI:10.1038/ng.2640
Reference
PMID:16518403 (C2 CFB)
  Authors
Gold B, Merriam JE, Zernant J, Hancox LS, Taiber AJ, Gehrs K, Cramer K, Neel J, Bergeron J, Barile GR, Smith RT, Hageman GS, Dean M, Allikmets R
  Title
Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration.
  Journal
Nat Genet 38:458-62 (2006)
DOI:10.1038/ng1750
Reference
PMID:24036952 (C9)
  Authors
Seddon JM, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, Goldstein JI, Triebwasser M, Anderson HE, Zerbib J, Kavanagh D, Souied E, Katsanis N, Daly MJ, Atkinson JP, Raychaudhuri S
  Title
Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.
  Journal
Nat Genet 45:1366-70 (2013)
DOI:10.1038/ng.2741
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