Abstract
The current review is focussing different factors that contribute and directly correlate to the onset and progression of Age-related Macular Degeneration (AMD). In particular, the susceptibility to AMD due to genetic and non-genetic factors and the establishment of risk scores, based on the analysis of different genes to measure the risk of developing the disease. A correlation with the actual therapeutic landscape to treat AMD patients from the point of view of pharmacokinetics and pharmacogenetics is also exposed. Treatments commonly used, as well as different regimes of administration, will be especially important in trying to classify individuals as “responders” and “non-responders”. Analysis of different genes correlated with drug response and also the emerging field of microRNAs (miRNAs) as possible biomarkers for early AMD detection and response will be also reviewed.
This article aims to provide the reader a review of different publications correlated with AMD from the molecular and kinetic point of view as well as its commonly used treatments, major pitfalls and future directions that, to our knowledge, could be interesting to assess and follow in order to develop a personalized medicine model for AMD.
Keywords: Susceptibility, pharmacogenetics, pharmacokinetics, treatments, age-related macular degeneration, anti-VEGF.
[http://dx.doi.org/10.1016/S0039-6257(05)80092-X] [PMID: 7604360]
[http://dx.doi.org/S0042-96862004001100009] [PMID: 15640920]
[http://dx.doi.org/10.1124/mi.10.5.4] [PMID: 21045241]
[http://dx.doi.org/10.1016/j.survophthal.2006.05.001] [PMID: 16818082]
[http://dx.doi.org/10.1001/archophthalmol.2010.92] [PMID: 20547953]
[http://dx.doi.org/10.1016/j.preteyeres.2013.12.004] [PMID: 24374240]
[http://dx.doi.org/10.1001/archopht.123.3.321] [PMID: 15767473]
[http://dx.doi.org/10.1146/annurev-genom-090413-025610] [PMID: 24773320]
[http://dx.doi.org/10.1001/jama.2013.4997] [PMID: 23644932]
[http://dx.doi.org/10.1016/S0716-8640(10)70620-9]
[http://dx.doi.org/10.1016/j.ophtha.2010.07.011] [PMID: 20920825]
[http://dx.doi.org/10.1517/13543784.2015.961601] [PMID: 25243494]
[http://dx.doi.org/10.1056/NEJMoa1102673] [PMID: 21526923]
[http://dx.doi.org/10.1016/j.ophtha.2012.04.015] [PMID: 22578446]
[http://dx.doi.org/10.1126/science.1110591] [PMID: 15831718]
[http://dx.doi.org/10.1371/journal.pone.0107461] [PMID: 25203061]
[http://dx.doi.org/10.4161/rna.7.5.13216] [PMID: 20930520]
[http://dx.doi.org/10.1016/S0161-6420(00)00580-7] [PMID: 11297486]
[http://dx.doi.org/10.1016/S0002-9394(14)71036-0] [PMID: 9186125]
[http://dx.doi.org/10.1016/j.ophtha.2003.11.010] [PMID: 15234127]
[http://dx.doi.org/10.1155/2013/895147] [PMID: 24368940]
[http://dx.doi.org/10.1111/j.1469-1809.2010.00x] [PMID: 20374233]
[http://dx.doi.org/10.1111/ahg.12011] [PMID: 23577725]
[http://dx.doi.org/10.1080/13816810.2016.1237664] [PMID: 28095100]
[http://dx.doi.org/10.1001/archopht.119.10.1417] [PMID: 11594942]
[http://dx.doi.org/10.1093/ajcn/76.3.595] [PMID: 12198005]
[http://dx.doi.org/10.3390/nu5030750] [PMID: 23529076]
[http://dx.doi.org/10.1167/iovs.15-18637] [PMID: 26990164]
[http://dx.doi.org/10.1001/archopht.121.6.785] [PMID: 12796248]
[http://dx.doi.org/10.1167/iovs.09-4000] [PMID: 19933179]
[http://dx.doi.org/10.1016/j.preteyeres.2017.11.004] [PMID: 29197628]
[http://dx.doi.org/10.1016/S0161-6420(01)01049-1] [PMID: 11927430]
[http://dx.doi.org/10.1126/science.1109557] [PMID: 15761122]
[http://dx.doi.org/10.1093/hmg/ddi353] [PMID: 16174643]
[http://dx.doi.org/10.1038%2Fng.2578] [PMID: 23455636]
[http://dx.doi.org/10.1073/pnas.0501536102] [PMID: 15870199]
[http://dx.doi.org/10.1038/ng1750] [PMID: 16518403]
[http://dx.doi.org/10.1038/ng1871] [PMID: 16936733]
[http://dx.doi.org/10.1056/NEJMoa072618] [PMID: 17634448]
[http://dx.doi.org/10.1038/ng.2741] [PMID: 24036952]
[http://dx.doi.org/10.1167/iovs.11-8425] [PMID: 22190594]
[http://dx.doi.org/10.1093/aje/kwj279] [PMID: 16916985]
[http://dx.doi.org/10.1167/iovs.05-1430] [PMID: 16936080]
[PMID: 10634626]
[http://dx.doi.org/10.1126/science.1133811] [PMID: 17053109]
[http://dx.doi.org/10.1016/j.visres.2007.10.014] [PMID: 18206206]
[http://dx.doi.org/10.4161/cc.6.9.4157] [PMID: 17426452]
[PMID: 23761723]
[http://dx.doi.org/10.1038/ng.3448] [PMID: 26691988]
[http://dx.doi.org/10.1016/j.optom.2013.07.002]
[http://dx.doi.org/10.1111/j.1755-3768.2010.02040.x] [PMID: 21106043]
[http://dx.doi.org/10.1186/1471-2350-12-58] [PMID: 21521525]
[http://dx.doi.org/10.1016/j.ajo.2010.08.048] [PMID: 21236409]
[http://dx.doi.org/10.1111/aos.12799] [PMID: 26154559]
[http://dx.doi.org/10.1016/j.ophtha.2008.10.018] [PMID: 19118696]
[http://dx.doi.org/10.1056/NEJMoa054481] [PMID: 17021318]
[http://dx.doi.org/10.1016/j.ajo.2009.01.024] [PMID: 19376495]
[http://dx.doi.org/10.1016/j.ophtha.2014.07.041] [PMID: 25227499]
[http://dx.doi.org/10.1016/j.oret.2016.12.004] [PMID: 31047517]
[http://dx.doi.org/10.1016/j.ophtha.2013.08.011] [PMID: 24084500]
[http://dx.doi.org/10.18553/jmcp.2018.24.2-a.s3] [PMID: 29383980]
[http://dx.doi.org/10.1111/aos.13031] [PMID: 27009503]
[http://dx.doi.org/10.1111/aos.13356] [PMID: 28139082]
[http://dx.doi.org/10.1016/S0365-6691(12)70047-3] [PMID: 23380436]
[http://dx.doi.org/10.1007/s40123-017-0087-5] [PMID: 28451952]
[http://dx.doi.org/10.1016/j.ajo.2007.01.028] [PMID: 17386270]
[http://dx.doi.org/10.1016/j.ajo.2013.06.020] [PMID: 23938122]
[http://dx.doi.org/10.1136/bjophthalmol-2015-306771] [PMID: 25957377]
[http://dx.doi.org/10.1167/iovs.15-16418] [PMID: 26305529]
[http://dx.doi.org/10.1016/j.preteyeres.2010.04.003] [PMID: 20452456]
[http://dx.doi.org/10.1167/iovs.12-10260] [PMID: 23361508]
[http://dx.doi.org/10.1097/IAE.0000000000001493] [PMID: 28106709]
[http://dx.doi.org/10.1016/j.ajo.2008.05.036] [PMID: 18635152]
[http://dx.doi.org/10.1097/IAE.0b013e318217373c] [PMID: 21738089]
[http://dx.doi.org/10.1586/17512433.2014.884458] [PMID: 24483136]
[http://dx.doi.org/10.1136/bjophthalmol-2014-305252] [PMID: 25001321]
[http://dx.doi.org/10.1016/j.ajo.2018.08.026] [PMID: 30148987]
[http://dx.doi.org/10.1038/eye.2017.187] [PMID: 28937147]
[http://dx.doi.org/10.1016/j.exer.2011.09.002] [PMID: 21933673]
[http://dx.doi.org/10.2147/DDDT.S67536] [PMID: 25960634]
[http://dx.doi.org/10.29200/acsmedchemrev-v51.ch16]
[http://dx.doi.org/10.1016/j.ophtha.2019.04.017] [PMID: 30986442]
[http://dx.doi.org/10.3928/23258160-20181203-01] [PMID: 30566697]
[http://dx.doi.org/10.22608/APO.2017258] [PMID: 28933517]
[http://dx.doi.org/10.1016/j.ophtha.2005.08.014] [PMID: 16325708]
[http://dx.doi.org/10.1136/bjophthalmol-2013-304267] [PMID: 24457363]
[http://dx.doi.org/10.1167/iovs.14-14803] [PMID: 25813999]
[http://dx.doi.org/10.1038/srep14517] [PMID: 26411831]
[http://dx.doi.org/10.1136/bjo.2010.193680] [PMID: 21558292]
[http://dx.doi.org/10.1007/s00417-014-2585-7] [PMID: 24522370]
[http://dx.doi.org/10.2217/pgs.13.43] [PMID: 23570466]
[http://dx.doi.org/10.1016/j.ophtha.2013.10.047] [PMID: 24365177]
[http://dx.doi.org/10.1167/iovs.10-6550] [PMID: 21245410]
[http://dx.doi.org/10.3109/02713683.2015.1067325] [PMID: 26398858]
[http://dx.doi.org/10.1007/s40291-018-0332-1] [PMID: 29700787]
[http://dx.doi.org/10.2147/OPTH.S39635] [PMID: 24143065]
[http://dx.doi.org/10.1016/j.ophtha.2012.11.037] [PMID: 23337555]
[http://dx.doi.org/10.1016/j.ophtha.2013.07.046] [PMID: 24070809]
[http://dx.doi.org/10.1016/j.ophtha.2014.02.025] [PMID: 24813631]
[http://dx.doi.org/10.1001/jamaophthalmol.2014.109] [PMID: 24652518]
[PMID: 25558172]
[http://dx.doi.org/10.1097/IAE.0000000000000466] [PMID: 25635578]
[http://dx.doi.org/10.4161/gmic.20168] [PMID: 22572830]
[http://dx.doi.org/10.1007/s13238-018-0546-3] [PMID: 29725936]
[http://dx.doi.org/10.1038/srep40826] [PMID: 28094305]
[http://dx.doi.org/10.15252/emmm.201606531] [PMID: 27861126]
[http://dx.doi.org/10.3389/fmicb.2018.00061] [PMID: 29441049]
[http://dx.doi.org/10.1007/978-3-319-75402-4_53] [PMID: 29721973]
[http://dx.doi.org/10.3390/nu10111677] [PMID: 30400586]
[http://dx.doi.org/10.1038/nature03315] [PMID: 15685193]
[http://dx.doi.org/10.1167/iovs.10-6165] [PMID: 21330653]
[http://dx.doi.org/10.3390/ijms18122659] [PMID: 29292750]
[http://dx.doi.org/10.1101/gad.1811209] [PMID: 19684108]
[http://dx.doi.org/10.1136/jmedgenet-2016-104266] [PMID: 28003323]
[http://dx.doi.org/10.3390/ijms17040478] [PMID: 27043545]
[http://dx.doi.org/10.1093/hmg/ddt156] [PMID: 23562822]
[http://dx.doi.org/10.1007/s11033-014-3320-5] [PMID: 24623407]
[http://dx.doi.org/10.2147/IJN.S140275] [PMID: 29089757]
[http://dx.doi.org/10.1038/ng1590] [PMID: 15965474]
[http://dx.doi.org/10.1016/j.cell.2004.12.035] [PMID: 15652477]
[PMID: 25221421]
[http://dx.doi.org/10.12659/MSM.893697] [PMID: 26366973]
[http://dx.doi.org/10.3389/fphar.2017.00168] [PMID: 28424619]
[http://dx.doi.org/10.1093/nar/gkq354] [PMID: 20453028]
[http://dx.doi.org/10.18632/oncotarget.8280] [PMID: 27015561]
[http://dx.doi.org/10.1016/j.survophthal.2013.03.009] [PMID: 24332379]
[http://dx.doi.org/10.1016/j.ophtha.2007.09.012] [PMID: 18054637]
[http://dx.doi.org/10.1016/j.ophtha.2007.01.017] [PMID: 17467524]
[http://dx.doi.org/10.1167/iovs.04-0601] [PMID: 15671306]
[http://dx.doi.org/10.1001/jamaophthalmol.2015.4070] [PMID: 26513684]
[http://dx.doi.org/10.22608/APO.2017495] [PMID: 29405046]
[http://dx.doi.org/10.1167/iovs.06-1171] [PMID: 17525217]