Figure 9

Possible LAMP-2/Lysosomal Inhibition Model of Pathogenesis of AMD. An unknown cause results in loss of the protective glycocalyx of LAMP-2. Proteolysis of LAMP-2 occurs. Loss of LAMP-2 results in either 1) A pH shift and loss of acidity of lysosome, 2) dynein no longer moving late phagosome to microtubule sorting center near Golgi for fusion with lysosome or 3) perturbation of M6PR/Rab recycling such that M6PR/Rab7 does not tag late endosomes. The loss of functionality of M6PR/Rab7 results in a lack of phagosome lysosome-fusion. Any of these results in loss of the lysosome's ability to degrade intra- and extracellular material. Subsequently, undegraded material is oxidized, turning to lipofuscin. Ultimately, the combination of oxidative stress, Fe+ accumulation, senile mitochondria and decrease in ATP results in inefficient turnover of organelles and increased inhibition of lysosomes. RPE death triggers photoreceptor and macula death.