Predictive, preventive and personalised medicine for age-related macular degeneration
تعليق: نظرية مضخات البروتون وضمور الشبكية المصاحب للتعمر.--احمد شوقي محمدين 19:40، 3 نوفمبر 2016 (ت ع م)
EPMA J. 2010 Jun; 1(2): 245–251.
Published online 2010 May 23. doi: 10.1007/s13167-010-0017-2
PMCID: PMC3405316
Predictive, preventive and personalised medicine for age-related macular degeneration
Pascal W. Haslercorresponding author and Josef Flammer
Lipofuscin and vascular endothelial growth factor (VEGF)
In the pathogenesis of AMD many mechanism are discussed. Regarding the two main forms, dry and wet AMD, the formation of lipofuscin plays an important role for the non-neovascular form and pro- and antiangiogenic factors more for the neovascular form. Lipofuscin is considered one of the ageing pigments, found in the liver, kidney, heart muscle, adrenals, nerve cells and pigment epithelium of the eye. It is specifically arranged around the nucleus, and is a type of lipochrome. Lipofuscin accumulation in the retinal pigment epithelium is associated with various blinding retinal diseases, including AMD. The major lipofuscin fluorophor A2-E is thought to play the most important pathogenetic role. It has been shown that A2-E severely impairs lysosomal function of RPE cells as a potent inhibitor of the ATP-driven proton pump located in the lysosomal membrane. Such inhibition of proton transport to the lysosomal lumen results in an increase of the lysosomal pH with subsequent inhibition of lysosomal hydrolases. An essential task of the lysosomal apparatus of retinal pigment epithelium cells for normal photoreceptor function is phagocytosis and degradation of membranous discs shed from photoreceptor outer segments and of biomolecules from autophagy. When lysosomes of cultured retinal pigment epithelium cells were experimentally loaded with A2-E, there was an intracellular accumulation of exogenously added photoreceptor outer segments. Moreover, the autophagic sequestration of cytoplasmic material was also markedly reduced after A2-E loading. These data support the hypothesis that A2-E-induced lysosomal dysfunction contributes to the pathogenesis of AMD [13].
