Aging, chronic oxidative stress, and inflammation are major pathogenic factors in the development and progression of age-related macular degeneration (AMD) with the loss of retinal pigment epithelium (RPE). The human RPE contains a subpopulation of progenitors (i.e., RPE stem cells—RPESCs) whose role in the RPE homeostasis is under investigation. We evaluated the paracrine effects of mature RPE cells exposed to oxidative stress (H2O2) on RPESCs behavior through co-cultural, morphofunctional, and bioinformatic approaches. RPESCs showed a decline in proliferation, an increase of the senescence-associated β-galactosidase activity, the acquisition of a senescent-like secretory phenotype (SASP), and the reduction of their stemness and differentiation competencies. IL-6 and Superoxide Dismutase 2 (SOD2) seem to be key molecules in RPESCs response to oxidative stress. Our results get insight into stress-induced senescent-associated molecular mechanisms implicated in AMD pathogenesis. The presence of chronic oxidative stress in the microenvironment reduces the RPESCs abilities, inducing and/or maintaining a pro-inflammatory retinal milieu that in turn could affect AMD onset and progression.
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Age-related macular degeneration
Cellular retinaldehyde-binding protein
Dulbecco's modified eagle medium
Fetal bovine serum
Human retinal pigment epithelial cells
Kruppel-like factor 4
Mesenchymal stromal cells
Microphthalmia-associated transcription factor
Orthodenticle homeobox 2
Paired box 6
Minimum essential medium eagle
Pigment-epithelium derived factor
Retinal pigment epithelial cell growth medium
Retinal pigment epithelial progenitor cells
Retinal pigment epithelium
Retinal pigment epithelium-specific 65 kDa protein
Senescence-associated secretory phenotype
SRY-box transcription factor 2
Superoxide dismutase 2
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This study was supported by a Grant of Università Politecnica delle Marche to Monica Mattioli-Belmonte.
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Lazzarini, R., Nicolai, M., Lucarini, G. et al. Oxidative stress in retinal pigment epithelium impairs stem cells: a vicious cycle in age-related macular degeneration. Mol Cell Biochem (2021). https://doi.org/10.1007/s11010-021-04258-3
- Retinal pigment epithelium
- Stem cells
- Oxidative stress
- Age-related macular degeneration (AMD)
- Senescence-associated secretory phenotype (SASP)