Research Paper Volume 6, Issue 12 pp 1064—1075

Figure 4. An example of how multiple pathways are activated and down-regulated during AMD.

This figure also serves as a working hypothesis for the pathogenesis of AMD. Proposed steps and interactions are as follows: A. Environmental Stress in the form of aging, obesity, inflammation, or diet causes B. senescence and loss of proliferation of the retinal pigment epithelial cells leading to C. activation of the MAPK, ERK, p38 and AKT pathways in the cytoplasmic components of the cells. This cellular senescence also has several consequences, primary of which are D. upregulation of the SASP, interleukin, and inflammatory cytokine networks, and E. downregulation of the caspase cascade and mitochondrial apoptosis. These pathways also interact; for example the upregulation of the SASP, interleukin, and inflammatory cytokine pathways causes downregulation of the caspase and mitochondrial apoptosis pathways. Green arrows represent upregulated pathways, red arrows represent downregulated pathways, and blue dotted arrows represent connected pathways.