Progress in defining the molecular biology of age related macular degeneration.
Age related macular degeneration (AMD) is an extremely prevalent complex genetic disorder. Its incidence rises exponentially in the elderly to a frequency of 1 in 2 in the general population by age 85. It affects approximately 25 million people and is the commonest cause of irreversible visual loss in the Western world. It is therefore a major public health problem. However, until recently its aetiology was unknown. Our understanding of both the molecular biology of AMD and the relevant clinical treatments has progressed dramatically in the last 2 years. Two genes of large effect have been identified which together contribute to over 70% of the population attributable risk of AMD. Treatments which inhibit expression of vascular endothelial growth factor have been developed which can rescue vision in the "wet" form of the disease. The association of complement factor H with AMD highlights the importance of the alternative complement pathway in the development of AMD whilst the pathophysiology of the serine protease HTRA1 is now under intensive study. This review will give an insight into these developments and will summarise our current knowledge of the molecular biology of AMD.
Clinical Neurosciences Division, University of Southampton, Southampton General Hospital, Southampton, SO16 6YD, UK. a.j.lotery@soton.ac.uk
Andrew
A
Lotery
Dorothy
D
Trump
D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000818:Animals; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration / Q000145:classification / Q000209:etiology / Q000235:genetics* / Q000628:therapy; D008967:Molecular Biology; D009154:Mutation; D010641:Phenotype; D015593:Retinal Drusen / Q000209:etiology / Q000276:immunology; D012307:Risk Factors; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics
C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters; C119630:EFEMP1 protein, human; D016326:Extracellular Matrix Proteins; D042461:Vascular Endothelial Growth Factor A; D017242:Complement Factor H; D011415:Complement Factor B