Keypathophysiologic pathways in age-related macular disease.
OBJECTIVE
To review current knowledge of key pathogenetic pathways in age-related macular disease (AMD).


METHODS
Experimental evidence and clinical observations are reviewed.


RESULTS
A number of common downstream pathophysiologic pathways appear to be relevant in AMD manifestations irrespective of primary heterogeneous etiologies. These include sequelae of oxidative damage, retinal pigment epithelium (RPE) cell dysfunction with accumulation of lipofuscin and impairment of lysosomal functions, deposition of subsequently incompletely degraded material at the basal RPE cell side and alterations in Bruch's membrane extracellular matrix, immunologic responses to extracellular material (drusen) with subsequent growth of drusen, induction of choroidal neovascularization as a result of imbalance between anti-angiogenetic and proangiogenetic factors as well as cell death (geographic atrophy) without prior neovascular events.


CONCLUSIONS
Understanding is expanding regarding the sequence of events that lead to early and late lesions in AMD. Therapeutic approaches that focus on the molecular mechanisms are more likely to succeed than currently available treatment options as exemplified by the management of choroidal neovascularisations.
Department of Ophthalmology, University of Bonn, Ernst-Abbestrasse 2, 53127 Bonn, Germany.
Felix
F
Roth
Almut
A
Bindewald
Frank G
FG
Holz
D000818:Animals; D016570:Bruch Membrane / Q000503:physiopathology; D006801:Humans; D008062:Lipofuscin / Q000378:metabolism; D008268:Macular Degeneration / Q000209:etiology* / Q000503:physiopathology; D018384:Oxidative Stress; D015593:Retinal Drusen / Q000209:etiology
D008062:Lipofuscin