title: Pharmacogenetics of antiangiogenic and antineovascular therapies of age-related macular degeneration.
abstract: Age-related macular degeneration (AMD), the most common age-related disease causing irreversible visual loss in industrialized countries, is a complex and multifactorial illness. Researchers have found components of the complement alternative pathway inside drusen and Bruch's membrane of AMD patients, underlying a possible important role of complement factor H in the pathogenesis of AMD. The neovascular (wet) AMD is the most destructive form and it is characterized by invasion of new blood vessels into subretinal spaces with subsequent exudation and bleeding, resulting in scarring of the macular region and loss of the central vision. The hallmark of the neovascular form is the choroidal neovascularization, where VEGF-A has an important role in the pathogenesis of the disease. SNPs of these genes have recently been investigated as potential pharmacogenetic markers of the antiangiogenic and antineovascular therapy of AMD, which includes verteporfin photodynamic therapy and anti-VEGF-A drugs, such as pegaptanib, bevacizumab and ranibizumab. The CFH rs1061170 CT and TT genotypes have been associated with an improvement of visual acuity in bevacizumab or ranibizumab treated patients, whereas patients harboring VEGF-A rs699946 G allele responded better to bevacizumab-based therapy if compared with patients carrying the A allele. In conclusion, the discovery of pharmacogenetic markers for the personalization of the antiangiogenic and/or antineovascular therapy could be, in the future, a key issue in ophthalmology to obtain a personalization of the therapy and to avoid unnecessary costs and adverse drug reactions.
authors: Division of Pharmacology, Department of Internal Medicine, University of Pisa, Via Roma, 55-56125, Pisa, Italy.
authors: Elisa
authors: E
authors: Agosta
authors: Stefano
authors: S
authors: Lazzeri
authors: Paola
authors: P
authors: Orlandi
authors: Michele
authors: M
authors: Figus
authors: Anna
authors: A
authors: Fioravanti
authors: Teresa
authors: T
authors: Di Desidero
authors: Maria Sole
authors: MS
authors: Sartini
authors: Marco
authors: M
authors: Nardi
authors: Romano
authors: R
authors: Danesi
authors: Guido
authors: G
authors: Bocci
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D001808:Blood Vessels / Q000254:growth & development / Q000473:pathology; D017242:Complement Factor H / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D010778:Photochemotherapy; D020641:Polymorphism, Single Nucleotide; D011166:Porphyrins / Q000008:administration & dosage*; D057285:Precision Medicine; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000077362:Verteporfin; D057135:Wet Macular Degeneration / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D011166:Porphyrins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D000077362:Verteporfin; D017242:Complement Factor H