scholarly journals In Vitro Maturation of Retinal Pigment Epithelium Is Essential for Maintaining High Expression of Key Functional Genes

2020 ◽  
Vol 21 (17) ◽  
pp. 6066
Author(s):  
Abdullah Al-Ani ◽  
Saud Sunba ◽  
Bilal Hafeez ◽  
Derek Toms ◽  
Mark Ungrin
Keyword(s):  
Retinal Pigment Epithelium ◽  
Single Cells ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Mrna Levels ◽  
Age Related ◽  
Rpe Transplantation ◽  
And Function

Age-related macular degeneration (AMD) is the leading cause of blindness in the industrialized world. AMD is associated with dysfunction and atrophy of the retinal pigment epithelium (RPE), which provides critical support for photoreceptor survival and function. RPE transplantation is a promising avenue towards a potentially curative treatment for early stage AMD patients, with encouraging reports from animal trials supporting recent progression toward clinical treatments. Mature RPE cells have been reported to be superior, but a detailed investigation of the specific changes in the expression pattern of key RPE genes during maturation is lacking. To understand the effect of maturity on RPE, we investigated transcript levels of 19 key RPE genes using ARPE-19 cell line and human embryonic stem cell-derived RPE cultures. Mature RPE cultures upregulated PEDF, IGF-1, CNTF and BDNF—genes that code for trophic factors known to enhance the survival and function of photoreceptors. Moreover, the mRNA levels of these genes are maximized after 42 days of maturation in culture and lost upon dissociation to single cells. Our findings will help to inform future animal and human RPE transplantation efforts.

scholarly journals Retinal Pigment Epithelium Replacement Therapy for Age-Related Macular Degeneration: Are We There Yet?

2020 ◽  
Vol 60 (1) ◽  
pp. 553-572 ◽  
Author(s):  
Ruchi Sharma ◽  
Devika Bose ◽  
Arvydas Maminishkis ◽  
Kapil Bharti
Keyword(s):  
Retinal Pigment Epithelium ◽  
Macular Degeneration ◽  
Primary Outcome ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Age Related ◽  
Retinal Photoreceptors ◽  
Rpe Transplantation ◽  
Potential Therapeutics

Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published clinical and preclinical studies have tested PSC-derived RPE as a potential treatment for AMD. Multiple approaches have been used to manufacture RPE cells, to validate them functionally, to confirm their safety profile, and to deliver them to patients either as suspension or as a monolayer patch. Since most of these studies are at an early regulatory approval stage, the primary outcome has been to determine the safety of RPE transplants in patients. However, preliminary signs of efficacy were observed in a few patients. Here, we review the current progress in the PSC-derived RPE transplantation field and provide a comparative assessment of various approaches under development as potential therapeutics for AMD.

scholarly journals Phase 1 clinical study of an embryonic stem cell–derived retinal pigment epithelium patch in age-related macular degeneration

2018 ◽  
Vol 36 (4) ◽  
pp. 328-337 ◽  
Author(s):  
Lyndon da Cruz ◽  
Kate Fynes ◽  
Odysseas Georgiadis ◽  
Julie Kerby ◽  
Yvonne H Luo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Clinical Study ◽  
Retinal Pigment Epithelium ◽  
Embryonic Stem Cell ◽  
Pigment Epithelium ◽  
Phase 1 ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Age Related

scholarly journals Development-related mitochondrial properties of retinal pigment epithelium cells derived from hEROs

2021 ◽  
Vol 14 (8) ◽  
pp. 1138-1150
Author(s):  
Hao-Jue Xu ◽  
◽  
Ting Zou ◽  
Zheng-Qin Yin ◽  
◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Embryonic Stem ◽  
Age Related Macular Degeneration ◽  
Level Energy ◽  
Rpe Cells ◽  
Age Related ◽  
High Level

AIM: To explore the temporal mitochondrial characteristics of retinal pigment epithelium (RPE) cells obtained from human embryonic stem cells (hESC)-derived retinal organoids (hEROs-RPE), to verify the optimal period for using hEROs-RPE as donor cells from the aspect of mitochondria and to optimize RPE cell-based therapeutic strategies for age-related macular degeneration (AMD). METHODS: RPE cells were obtained from hEROs and from spontaneous differentiation (SD-RPE). The mitochondrial characteristics were analyzed every 20d from day 60 to 160. Mitochondrial quantity was measured by MitoTracker Green staining. Transmission electron microscopy (TEM) was adopted to assess the morphological features of the mitochondria, including their distribution, length, and cristae. Mitochondrial membrane potentials (MMPs) were determined by JC-1 staining and evaluated by flow cytometry, reactive oxygen species (ROS) levels were evaluated by flow cytometry, and adenosine triphosphate (ATP) levels were measured by a luminometer. Differences between two groups were analyzed by the independent-samples t-test, and comparisons among multiple groups were made using one-way ANOVA or Kruskal-Wallis H test when equal variance was not assumed. RESULTS: hEROs-RPE and SD-RPE cells from day 60 to 160 were successfully differentiated from hESCs and expressed RPE markers (Pax6, MITF, Bestrophin-1, RPE65, Cralbp). RPE features, including a cobblestone-like morphology with tight junctions (ZO-1), pigments and microvilli, were also observed in both hEROs-RPE and SD-RPE cells. The mitochondrial quantities of hEROs-RPE and SD-RPE cells both peaked at day 80. However, the cristae of hEROs-RPE mitochondria were less mature and abundant than those of SD-RPE mitochondria at day 80, with hEROs-RPE mitochondria becoming mature at day 100. Both hEROs-RPE and SD-RPE cells showed low ROS levels from day 100 to 140 and maintained a normal MMP during this period. However, hEROs-RPE mitochondria maintained a longer time to produce high levels of ATP (from day 120 to 140) than SD-RPE cells (only day 120). CONCLUSION: hEROs-RPE mitochondria develop more slowly and maintain a longer time to supply high-level energy than SD-RPE mitochondria. From the mitochondrial perspective, hEROs-RPE cells from day 100 to 140 are an optimal cell source for treating AMD.

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.

scholarly journals 4-(Phenylsulfanyl) Butan-2-One Attenuates the Inflammatory Response Induced by Amyloid-β Oligomers in Retinal Pigment Epithelium Cells

Marine Drugs ◽  
2020 ◽  
Vol 19 (1) ◽  
pp. 1
Author(s):  
Peeraporn Varinthra ◽  
Shun-Ping Huang ◽  
Supin Chompoopong ◽  
Zhi-Hong Wen ◽  
Ingrid Y. Liu
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Amyloid Β ◽  
Age Related Macular Degeneration ◽  
Epithelial Cell Line ◽  
Age Related ◽  
Tnf Α ◽  
Cox 2

Age-related macular degeneration (AMD) is a progressive eye disease that causes irreversible impairment of central vision, and effective treatment is not yet available. Extracellular accumulation of amyloid-beta (Aβ) in drusen that lie under the retinal pigment epithelium (RPE) has been reported as one of the early signs of AMD and was found in more than 60% of Alzheimer’s disease (AD) patients. Extracellular deposition of Aβ can induce the expression of inflammatory cytokines such as IL-1β, TNF-α, COX-2, and iNOS in RPE cells. Thus, finding a compound that can effectively reduce the inflammatory response may help the treatment of AMD. In this research, we investigated the anti-inflammatory effect of the coral-derived compound 4-(phenylsulfanyl) butan-2-one (4-PSB-2) on Aβ1-42 oligomer (oAβ1-42) added to the human adult retinal pigment epithelial cell line (ARPE-19). Our results demonstrated that 4-PSB-2 can decrease the elevated expressions of TNF-α, COX-2, and iNOS via NF-κB signaling in ARPE-19 cells treated with oAβ1-42 without causing any cytotoxicity or notable side effects. This study suggests that 4-PSB-2 is a promising drug candidate for attenuation of AMD.

scholarly journals Retinal Pigment Epithelium Expressed Toll-like Receptors and Their Potential Role in Age-Related Macular Degeneration

2021 ◽  
Vol 22 (16) ◽  
pp. 8387
Author(s):  
Alexa Klettner ◽  
Johann Roider
Keyword(s):  
Retinal Pigment Epithelium ◽  
Inflammatory Response ◽  
Macular Degeneration ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Age Related Macular Degeneration ◽  
Current Status ◽  
Toll Like Receptors ◽  
Cell Degeneration ◽  
Age Related

(1) Background: Inflammation is a major pathomechanism in the development and progression of age-related macular degeneration (AMD). The retinal pigment epithelium (RPE) may contribute to retinal inflammation via activation of its Toll-like receptors (TLR). TLR are pattern recognition receptors that detect the pathogen- or danger-associated molecular pattern. The involvement of TLR activation in AMD is so far not understood. (2) Methods: We performed a systematic literature research, consulting the National Library of Medicine (PubMed). (3) Results: We identified 106 studies, of which 54 were included in this review. Based on these studies, the current status of TLR in AMD, the effects of TLR in RPE activation and of the interaction of TLR activated RPE with monocytic cells are given, and the potential of TLR activation in RPE as part of the AMD development is discussed. (4) Conclusion: The activation of TLR2, -3, and -4 induces a profound pro-inflammatory response in the RPE that may contribute to (long-term) inflammation by induction of pro-inflammatory cytokines, reducing RPE function and causing RPE cell degeneration, thereby potentially constantly providing new TLR ligands, which could perpetuate and, in the long run, exacerbate the inflammatory response, which may contribute to AMD development. Furthermore, the combined activation of RPE and microglia may exacerbate neurotoxic effects.

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