Abstract
Regenerative medicine approaches based on mesenchymal stem cells (MSCs) are being investigated to treat several aging-associated diseases, including age-related macular degeneration (AMD). Loss of retinal pigment epithelium (RPE) cells occurs early in AMD, and their transplant has the potential to slow disease progression.The human RPE contains a subpopulation of cells - adult RPE stem cells (RPESCs) – that are capable of self-renewal and of differentiating into RPE cells in vitro. However, age-related MSC changes involve loss of function and acquisition of a senescence-associated secretory phenotype (SASP), which can contribute to the maintenance of a chronic state of low-grade inflammation in tissues and organs.In a previous study we isolated, characterized, and differentiated RPESCs. Here, we induced replicative senescence in RPESCs and tested their acquisition of the senescence phenotype and the SASP as well as the differentiation ability of young and senescent RPESCs.Senescent RPESCs showed a significantly reduced proliferation ability, high senescence-associated β-galactosidase activity, and SASP acquisition. RPE-specific genes were downregulated and p21 and p53 protein expression was upregulated.These findings document the effects of senescence and SASP acquisition on RPESC differentiation ability and highlight the need for a greater understanding of their role in AMD pathogenesis.
Highlights
Age-related macular degeneration (AMD) is an eye disorder affecting the elderly which can induce an irreversible loss of central visual function [1]
mesenchymal stem cells (MSCs) enter replicative senescence after a limited number of cell divisions, a fact that needs to be considered in experiments involving cell cultures, especially in investigations of regenerative medicine approaches
Human RPE stem cells (RPESCs) have been identified as a stem-cell like population, they are unable to differentiate into mature retinal pigment epithelium (RPE) cells, replacing those that are lost due to age-related macular degeneration (AMD)
Summary
Age-related macular degeneration (AMD) is an eye disorder affecting the elderly which can induce an irreversible loss of central visual function [1]. The Age-Related Eye Disease Study (AREDS) has classified AMD into early, intermediate, and late stage [6], while the Clinical Age-Related Maculopathy Staging (CARMS) system divides patients into five mutually exclusive categories based on slit-lamp assessment of clinical features [7]. In 2013, the Beckman Initiative for Macular Research Classification Committee proposed a new clinical www.aging-us.com classification based on the three AREDS stages: stage 1, normal, aging phenotype (small drusen < 63 μm without pigmentary changes); stage 2, early AMD with medium drusen (63 - 125 μm) and no pigmentary abnormalities; and stage 3, which is subdivided into intermediate – large drusen and/or pigmentary changes – and advanced – choroidal neovascularization (CNV, exudative or neovascular AMD) or geographic atrophy (GA; dry or non-exudative AMD) [8]. Anti-vascular endothelial growth factor (anti-VEGF) has long been the mainstay of treatment for neovascular AMD, whereas no effective treatment is available for the more common dry form [9,10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
