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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Vydáno v:	Molecular and cellular biochemistry Ročník 477; číslo 1; s. 67 - 77
Hlavní autoři:	Lazzarini, Raffaella, Nicolai, Michele, Lucarini, Guendalina, Pirani, Vittorio, Mariotti, Cesare, Bracci, Massimo, Mattioli-Belmonte, Monica
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Springer US 01.01.2022 Springer Springer Nature B.V
Témata:	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
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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	0300-8177 1573-4919 1573-4919
DOI:	10.1007/s11010-021-04258-3