age-related macular degeneration
Age-related macular degeneration (AMD) is a disease that destroys the macula (the central part of retina), severely regimenting a person’s normal sight. Current treatments include photodynamic therapy and photocoagulation.
Basal laminar drusen are hallmark lesions of AMD and consist of focal-inflammatory and/or immune-mediated depositions of extracellular material at the interface of the retinal pigment epithelium (RPE) and the Bruch membrane.
Etiology
Age-related macular degeneration (AMD) is a multifactorial disease that is strongly associated with the Tyr402His variant in the complement factor H (CFH) gene.
Susceptibilty loci (#12945014#, #12900797#)
1q31 (#15168325#)
chromosome 2
3p13 (#15168325#)
4q32 (#15168325#)
chromosome 6
chromosome 8
9q33
10q26 (#16080115#)
chromosome 12
chromosome 16
17q25 (#15168325#)
chromosome 22
chromosome X
Genes involved in susceptibility
fibuline-5 (FBLN5) (in ARMD3 MIM.608895)
CST3
CX3CR1
TLR4
VEGF
LRP6
MMP9
Animal models
Ccl-2(-/-)- knockout mice
Ccr-2(-/-)- knockout mice
The characterization of Ccl-2(-/-)- and Ccr-2(-/-)-knockout mice with features of AMD, coupled with a recently reported association of the gene encoding complement factor H with this disorder, suggests the involvement of macrophages and complement in the pathogenesis of this disease.
References
Jager RD, Mieler WF, Miller JW. Age-related macular degeneration. N Engl J Med. 2008 Jun 12;358(24):2606-17. PMID: #18550876#
de Jong PT. Age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1474-85. PMID: #17021323#
Anand A, Prabhakar S, Ambeti J. Molecular basis of AMD: current concepts and recent advances. Trends Mol Med. 2005 Jun 14; PMID: #15963761#
Tezel TH, Bora NS, Kaplan HJ. Pathogenesis of age-related macular degeneration. Trends Mol Med. 2004 Sep;10(9):417-20. PMID: #15350892#
Stone EM, Sheffield VC, Hageman GS. Molecular genetics of age-related macular degeneration. Hum Mol Genet. 2001 Oct 1;10(20):2285-92. PMID: #11673412#