KEGG DISEASE: Age-related macular degeneration

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 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
Pathway-based classification of diseases [BR:br08402]
Cellular process
  nt06535  Efferocytosis
   H00821  Age-related macular degeneration
  nt06527  Necroptosis
   H00821  Age-related macular degeneration
Immune system
  nt06513  Complement cascade
   H00821  Age-related macular degeneration
  nt06517  TLR signaling
   H00821  Age-related macular degeneration

Pathway

hsa04610

Complement and coagulation cascades

hsa04620

Toll-like receptor signaling pathway

hsa04217

Necroptosis

Network

nt06513 Complement cascade
nt06517 TLR signaling
nt06527 Necroptosis
nt06535 Efferocytosis

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]
Avacincaptad pegol sodium [DR:D11748]

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

PMID:18097986

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

PMID:17636773

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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Disease (15)   
   OMIM (15)   
Drug (6)   
   KEGG DRUG (6)   
Gene (35)   
   KEGG ORTHOLOGY (17)   
   KEGG GENES (18)   
Literature (18)   
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