Oxidative stress in retinal pigment epithelium impairs stem cells: a vicious cycle in age-related macular degeneration

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 r...

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Published in:Molecular and cellular biochemistry Vol. 477; no. 1; pp. 67 - 77
Main Authors: Lazzarini, Raffaella, Nicolai, Michele, Lucarini, Guendalina, Pirani, Vittorio, Mariotti, Cesare, Bracci, Massimo, Mattioli-Belmonte, Monica
Format: Journal Article
Language:English
Published: New York Springer US 01.01.2022
Springer
Springer Nature B.V
Subjects:
Age related diseases
Aging
Biochemistry
Biomedical and Life Sciences
Cardiology
Cell Line
Epithelium
Eye diseases
Functional morphology
Galactosidase
Homeostasis
Humans
Hydrogen peroxide
Hydrogen Peroxide - pharmacology
Inflammation
Interleukin 6
Interleukin-6 - metabolism
Life Sciences
Macular degeneration
Macular Degeneration - metabolism
Medical Biochemistry
Microenvironments
Molecular modelling
Oncology
Oxidative Stress
Paracrine signalling
Pathogenesis
Phenotypes
Progenitor cells
Retina
Retinal pigment epithelium
Retinal Pigment Epithelium - metabolism
Senescence
Stem cells
Stem Cells - metabolism
Superoxide
Superoxide dismutase
Superoxide Dismutase - metabolism
β-Galactosidase
Oxidative stress
Inflammation
Senescence-associated secretory phenotype (SASP)
Age-related macular degeneration (AMD)
Retinal pigment epithelium
Stem cells
ISSN:0300-8177, 1573-4919, 1573-4919
Online Access:Get full text
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Summary: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 (H 2 O 2 ) 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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ISSN:0300-8177
1573-4919
1573-4919
DOI:10.1007/s11010-021-04258-3