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Human amniotic epithelial stem cell-derived retinal pigment epithelium cells repair retinal degeneration

ABSTRACT: Human amniotic epithelial stem cell-derived retinal pigment epithelium cells repair retinal degeneration

PROVIDER: PRJNA748889 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15214336_1.fastq.gz	Fastqsanger.gz
	SRR15214336_2.fastq.gz	Fastqsanger.gz
	SRR15214337_1.fastq.gz	Fastqsanger.gz
	SRR15214337_2.fastq.gz	Fastqsanger.gz
	SRR15214338_1.fastq.gz	Fastqsanger.gz

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Human amniotic epithelial stem cell-derived retinal pigment epithelium cells repair retinal degeneration

Project description:Age-related macular degeneration (AMD), featured with dysfunction and loss of retinal pigment epithelium (RPE), is lacking efficient therapeutic approaches. According to our previous studies, human amniotic epithelial stem cells (hAESCs) may serve as a potential seed cell source of RPE cells for therapy because they have no ethical concerns, no tumorigenicity, and little immunogenicity. Herein, trichostatin A and nicotinamide can direct hAESCs differentiation into RPE like cells. The differentiated cells display the morphology, marker expression and cellular function of the native RPE cells, and noticeably express little MHC class II antigens and high level of HLA-G. Importantly, visual function and retinal structure of Royal College of Surgeon (RCS) rats, a classical animal model of retinal degeneration, were rescued after subretinal transplantation with the hAESCs-derived RPE like cells. We established a high-efficient, low-cost and safety-guaranteed system for generating functional RPE cells from hAESCs. These results suggest a novel and ideal therapeutic strategy for retinal degeneration diseases

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Whole genome methylation profiling of the retinal pigment epithelium of individuals with age-related macular degeneration

Project description:Illumina Infinium HumanMethylation450 BeadChip data from genomic DNA of retinal pigment epithelium from Age-related Macular Degeneration patients or age-matched controls.

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Functional Retinal Pigment Epithelium-like Cells from Human Fibroblasts

Project description:The retinal pigment epithelium (RPE) provides vital support to photoreceptor cells and its dysfunction is associated with the onset and progression of age-related macular degeneration (AMD). Surgical provision of RPE cells may ameliorate AMD and thus it would be valuable to develop sources of patient-matched RPE cells for this application of regenerative medicine. We describe here the generation of functional RPE-like cells from fibroblasts that represent an important step toward that goal. We identified candidate master transcriptional regulators of RPEs using a novel computational method and then used these regulators to guide exploration of the transcriptional regulatory circuitry of RPE cells and to reprogram human fibroblasts into RPE-like cells. The RPE-like cells share key features with RPEs derived from healthy individuals, including morphology, gene expression and function, and thus represent a step toward the goal of generating patient-matched RPE cells for treatment of macular degeneration. Expression analysis was performed on induced retinal pigment epithelium-like cells.

2015-09-23 | E-GEOD-64264 | biostudies-arrayexpress

Human Amniotic Epithelial Stem Cell-Derived Retinal Pigment Epithelium Cells Repair Retinal Degeneration.

Project description:Age-related macular degeneration (AMD), featured with dysfunction and loss of retinal pigment epithelium (RPE), is lacking efficient therapeutic approaches. According to our previous studies, human amniotic epithelial stem cells (hAESCs) may serve as a potential seed cell source of RPE cells for therapy because they have no ethical concerns, no tumorigenicity, and little immunogenicity. Herein, trichostatin A and nicotinamide can direct hAESCs differentiation into RPE like cells. The differentiated cells display the morphology, marker expression and cellular function of the native RPE cells, and noticeably express little MHC class II antigens and high level of HLA-G. Moreover, visual function and retinal structure of Royal College of Surgeon (RCS) rats, a classical animal model of retinal degeneration, were rescued after subretinal transplantation with the hAESCs-derived RPE like cells. Our study possibly makes some contribution to the resource of functional RPE cells for cell therapy. Subretinal transplantation of hAESCs-RPE could be an optional therapeutic strategy for retinal degeneration diseases.

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INFLAMMATION OF THE RETINAL PIGMENT EPITHELIUM DRIVES EARLY-ONSET PHOTORECEPTOR DEGENERATION IN MERTK-ASSOCIATED RETINITIS PIGMENTOSA

Project description:Severe, early-onset photoreceptor (PR) degeneration associated with MERTK mutations is thought to result from failed phagocytosis by retinal pigment epithelium (RPE). Notwithstanding, the severity and onset of PR degeneration in mouse models of Mertk ablation is determined by the hypomorphic expression or the loss of the Mertk paralog Tyro3. Here we find that loss of Mertk and reduced expression/loss of Tyro3 led to RPE inflammation, even before eye-opening. Incipient RPE inflammation cascaded to involve microglia activation and PR degeneration with monocyte infiltration. Inhibition of RPE inflammation with the JAK1/2 inhibitor ruxolitinib mitigated PR degeneration in Mertk -/- mice. Neither inflammation nor severe, early-onset PR degeneration were observed in mice with defective phagocytosis alone. Thus, inflammation drives severe, early-onset PR degeneration-associated with Mertk loss of function.

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Project description:Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration

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