scholarly journals Microphthalmia-Associated Transcription Factor in Senescence and Age-Related Diseases

Gerontology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Jian Zhang ◽  
Yi Mou ◽  
Hui Gong ◽  
Honghan Chen ◽  
Hengyi Xiao
Keyword(s):  
Transcription Factor ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Underlying Mechanism ◽  
Age Related ◽  
Damage Repair ◽  
Cycle Regulation ◽  
The Relationship ◽  
Epithelium Cells ◽  
Melanocytic Differentiation

Although microphthalmia-associated transcription factor (MITF) has been known for decades as a key regulator for melanocytic differentiation, recent studies expanded its other roles in multiple biological processes. Among these newfound roles, the relationship between MITF and aging is attractive; however, the underlying mechanism remains elusive. Here, we review the documented cues that highlight the implication of MITF in the aging process and particularly discuss the possible mechanisms underlying the participation of MITF in cellular senescence. First, it summarizes the association of MITF with melanocytic senescence, including the roles of MITF in cell cycle regulation, DNA damage repair, oxidative stress response, and the generation of senescence-associated secretory phenotype. Then, it collects the information involving MITF-related senescent changes in nonmelanocytes, such as retinal pigment epithelium cells, osteoclasts, and cardiomyocytes. This review may deepen the understanding of MITF function and be helpful to develop new strategies for improving geriatric health.

scholarly journals Scaffolds for retinal pigment epithelial cell transplantation in age-related macular degeneration

2017 ◽  
Vol 8 ◽  
pp. 204173141772084 ◽  
Author(s):  
Corina E White ◽  
Ronke M Olabisi
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Cell Monolayer ◽  
Age Related Macular Degeneration ◽  
Artificial Substrates ◽  
Age Related ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

In several retinal degenerative diseases, including age-related macular degeneration, the retinal pigment epithelium, a highly functionalized cell monolayer, becomes dysfunctional. These retinal diseases are marked by early retinal pigment epithelium dysfunction reducing its ability to maintain a healthy retina, hence making the retinal pigment epithelium an attractive target for treatment. Cell therapies, including bolus cell injections, have been investigated with mixed results. Since bolus cell injection does not promote the proper monolayer architecture, scaffolds seeded with retinal pigment epithelium cells and then implanted have been increasingly investigated. Such cell-seeded scaffolds address both the dysfunction of the retinal pigment epithelium cells and age-related retinal changes that inhibit the efficacy of cell-only therapies. Currently, several groups are investigating retinal therapies using seeded cells from a number of cell sources on a variety of scaffolds, such as degradable, non-degradable, natural, and artificial substrates. This review describes the variety of scaffolds that have been developed for the implantation of retinal pigment epithelium cells.

scholarly journals Inhibition of Proteasome Activity Upregulates IL-6 Expression in RPE Cells through the Activation of P38 MAPKs

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Tingyu Qin ◽  
Shasha Gao
Keyword(s):  
Proteasome Inhibitor ◽  
Culture Medium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Signal Pathways ◽  
Rpe Cells ◽  
Age Related ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

Purpose. As far as we know, during the development of age-related macular degeneration (AMD), the activity of proteasome in retinal pigment epithelium cells (RPE) gradually decreases. And a lot of research has shown that age-related macular degeneration is closely related to inflammation and autoimmune. Moreover, there are many cytokines (CKs) involved in the course of inflammation. In this study, we are going to investigate how the decrease of proteasome activity affects the production of interleukin-6 (IL-6) in human retinal pigment epithelium cells (ARPE-19). Methods. Cultured ARPE-19 was treated with or without MG132, a proteasome inhibitor, and the levels of IL-6 mRNA (messenger ribonucleic acid) in RPE at 1 h, 4 h, 8 h, and IL-6 protein in the culture medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were measured by real-time polymerase chain reaction (real-time PCR) and enzyme-linked immunosorbent assay (ELISA). The protein levels of MCP-1 (monocyte chemoattractant protein-1) in the culture medium at 2 h, 4 h, 6 h, 8 h, 10 h, and 12 h were also measured by ELISA. Then we tested which of cell signal pathways regulating the production of IL-6 were activated when we added MG132 into the medium by Western blot and electrophoretic mobility shift assays (EMSA). After that, we put the inhibitors of these activated cell signal pathways into the medium individually to see which inhibitor can counteract the effect of upregulating the levels of IL-6 in the culture medium of RPE. Results. MG132 decreased the secretion of MCP-1 in the culture medium of RPE, but it increased the expression of IL-6 mRNA in RPE and IL-6 protein level in the culture medium of RPE. MG132 treatment was also found to enhance the level of phosphorylated p38 mitogen-activated protein kinases (MAPKs) and c-Jun N-terminal Kinase (JNK) by Western blotting. More importantly, the effect of MG132 on upregulating the levels of IL-6 was inhibited by SB203580, an inhibitor of P38 MAP kinases. But the JNK inhibitor, SP600125, cannot prevent the effect of upregulating the levels of IL-6 by MG132 in the RPE culture medium. Conclusions. We concluded that the proteasome inhibitor, MG132, upregulates IL-6 production in RPE cells through the activation of P38 MAPKs.

scholarly journals Relationship between Oxidative Stress, Circadian Rhythms, and AMD

2016 ◽  
Vol 2016 ◽  
pp. 1-18 ◽  
Author(s):  
María Luisa Fanjul-Moles ◽  
Germán Octavio López-Riquelme
Keyword(s):  
Oxidative Stress ◽  
Circadian Rhythms ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Retinal Damage ◽  
Cell Organelles ◽  
Age Related ◽  
Exogenous Factors ◽  
The Relationship

This work reviews concepts regarding oxidative stress and the mechanisms by which endogenous and exogenous factors produce reactive oxygen species (ROS). It also surveys the relationships between oxidative stress, circadian rhythms, and retinal damage in humans, particularly those related to light and photodamage. In the first section, the production of ROS by different cell organelles and biomolecules and the antioxidant mechanisms that antagonize this damage are reviewed. The second section includes a brief review of circadian clocks and their relationship with the cellular redox state. In the third part of this work, the relationship between retinal damage and ROS is described. The last part of this work focuses on retinal degenerative pathology, age-related macular degeneration, and the relationships between this pathology, ROS, and light. Finally, the possible interactions between the retinal pigment epithelium (RPE), circadian rhythms, and this pathology are discussed.

scholarly journals Investigation of Differentiated Embryonic Stem Cells Growth on Optimized Porous Polymeric Bed with Fuzzy System

2021 ◽  
Author(s):  
Saleheh Shahmoradi ◽  
Fatemeh Yazdian ◽  
Amin Janghorbani ◽  
Leila Satarian ◽  
Farnaz Behroozi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

Introduction: Age-related macular degeneration (AMD) is one of the retina diseases in which retinal pigment epithelium cells are degraded and lead to blindness. Available treatments only slow down the progression of it. In this study, human embryonic stem cells (hESCs) differentiated into retinal pigment epithelium cells were cultured on a polycaprolactone scaffold. Methods: The optimization of the diameter of the produced scaffolds by electrospinning method was done using the fuzzy method for the first time. To improve cell adhesion and proliferation, related parameters to alkaline hydrolysis method were optimized and hydrophobic surface of scaffold was modified. After in vitro analysis, cells were cultured on different groups of scaffolds. In vivo analyses were done and cells culture on scaffolds observed. Results: The optimal parameters for the scaffold based on the fuzzy model were 18.1 kV for voltage, 0.07 g / ml for solution concentration and 115 nm for scaffold diameter, respectively. The immersion time of the scaffold in alkaline solution and concentration of solution were measured 97 min and 3.7 M, respectively. The treated scaffold had a higher degradation rate and water adsorption. MTT-Assay results showed that scaffolds with modified surfaces had a higher amount of cell viability and proliferation after 7 days. SEM image results confirmed this finding after almost two months. Additionally, the results of ICC test showed that after passing this time, cells kept their RPE and epithelium. Conclusion: Based on the results, the hydrolyzed scaffold is a suitable substrate for cell proliferation and can be a good option for AMD treatment.

Wheat alkylresorcinols protect human retinal pigment epithelial cells against H2O2-induced oxidative damage through Akt-dependent Nrf2/HO-1 signaling

2019 ◽  
Vol 10 (5) ◽  
pp. 2797-2804 ◽  
Author(s):  
Ziyuan Wang ◽  
Yiming Hao ◽  
Yu Wang ◽  
Jie Liu ◽  
Xiaoping Yuan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Retinal Pigment Epithelial ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Underlying Mechanism ◽  
Retinal Pigment Epithelial Cells ◽  
Pigment Epithelial ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells ◽  
Pigment Epithelial Cells

The protective effect of wheat alkylresorcinols (ARs) on human retinal pigment epithelium cells (ARPE-19) against oxidative stress and the possible underlying mechanism were investigated in this study.

scholarly journals In vivo imaging of retinal pigment epithelium cells in age related macular degeneration

2013 ◽  
Vol 4 (11) ◽  
pp. 2527 ◽  
Author(s):  
Ethan A. Rossi ◽  
Piero Rangel-Fonseca ◽  
Keith Parkins ◽  
William Fischer ◽  
Lisa R. Latchney ◽  
...  
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
In Vivo Imaging ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Pigment Epithelium Cells ◽  
Epithelium Cells

scholarly journals Identification of age-associated proteins and functional alterations in human primary retinal pigment epithelium cells

2021 ◽  
Author(s):  
jin xiuxiu ◽  
Liu Jingyang ◽  
Wang Weiping ◽  
Li Jiangfeng ◽  
Liu Guangming ◽  
...  
Keyword(s):  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Molecular Characteristics ◽  
Proteomic Data ◽  
Age Related ◽  
Clearance Mechanism ◽  
Associated Proteins ◽  
Age Range ◽  
Epithelium Cells ◽  
Molecular Picture

Background: Retinal pigmented epithelium (RPE) has essential functions to nourish and support the neural retina, and is of vital importance in the pathogenesis of age-related retinal degeneration. However, the exact molecular changes of RPE in aging remain poorly defined. Methods: We isolated human primary RPE (hRPE) cells from 18 eye donors distributed over a wide age range (10 - 67 years). A quantitative proteomic analysis was performed to analyze their intracellular and secreted protein changes, and potential age-associtated mechanisms were validated by ARPE-19 and hRPE cells. Results: Age-stage related subtypes and age-associtated proteins and functional alterations were revealed. Proteomic data and verifications showed that RNF123 and RNF149 related ubiquitin-mediated proteolysis might be an important clearance mechanism in elimination of oxidative damaged proteins in aged hRPE. In older hRPE cells, apoptotic signaling related pathways were up-regulated and endoplasmic reticulum organization was down-regulated both in intracellular and secreted proteome. Conclusions: This work paints a detailed molecular picture of human RPE in aging process and provides new insights for molecular characteristics of RPE in aging and related clinical retinal conditions.

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