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. Author manuscript; available in PMC: 2023 Sep 1.
Published in final edited form as: Exp Eye Res. 2022 Jul 4;222:109164. doi: 10.1016/j.exer.2022.109164

Fig. 3. Proposed mechanisms of elastin turnover in the pathogenesis of dry and wet AMD.

Fig. 3.

During AMD pathogenesis local inflammation or oxidative stress can upsurge the elastase secretion from RPE cells, infiltrating immune cells such as macrophages/neutrophils and microglia leading to elastin degradation and EDP generation. EDPs can bind to the GLB1 receptors present on the choroidal endothelial cells (Skeie et al., 2012). EDP binding to the endothelial cells can increase the MT1-MMP level (Robinet et al., 2005) and the phosphorylation of FAK/-PI3–K/Akt/mTOR (Gunda et al., 2013) pathway, leading to VEGF upregulation (Sounni et al., 2004), endothelial cell migration and pathological neovascularization. Collagen fragment α6(IV) NC1 can inhibit this elastin peptide mediated endothelial cell migration and angiogenesis (Gunda et al., 2013). Products of elastin degradation can also increase the autoantibody production and complement C3 overactivation (Annamalai et al., 2020), suggesting its possible role in RPE death and dry AMD pathogenesis. Abbreviations: RPE, Retinal Pigment Epithelium; MMP, matrix metalloproteinase; HTRA1, High-Temperature Requirement A Serine Peptidase 1; ELANE, Neutrophil Elastase/leukocyte elastase; EDP, Elastin Derived Peptides; GLB1, Galactosidase beta 1 receptor; MT1 MMP, Membrane Type 1 MMP; Collagen α6(IV) NC1, type IV collagen α-6 chain-derived non-collagenous domain; VEGF-A, Vascular Endothelial Growth Factor A; FAK/-PI3–K/Akt/mTOR, Focal adhesion kinase(FAK)/-phosphoinositide 3-kinase/protein kinase B (PI3K/AKT)/mammalian target of rapamycin (mTOR).