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THE IMMUNE RESPONSE MODULATES ZEBRAFISH RETINAL PIGMENT EPITHELIUM REGENERATION [macrophages]

ABSTRACT: THE IMMUNE RESPONSE MODULATES ZEBRAFISH RETINAL PIGMENT EPITHELIUM REGENERATION [macrophages]

PROVIDER: PRJNA649262 | ENA |

REPOSITORIES: ENA

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THE IMMUNE RESPONSE MODULATES ZEBRAFISH RETINAL PIGMENT EPITHELIUM REGENERATION [RPE]

Project description:THE IMMUNE RESPONSE MODULATES ZEBRAFISH RETINAL PIGMENT EPITHELIUM REGENERATION [RPE]

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THE IMMUNE RESPONSE MODULATES ZEBRAFISH RETINAL PIGMENT EPITHELIUM REGENERATION [macrophages]

Project description:Loss of the retinal pigment epithelium (RPE) due to dysfunction or disease can lead to blindness in humans. Harnessing the intrinsic ability of the RPE to self-repair is an attractive therapeutic strategy; however, mammalian RPE is limited in its regenerative capacity. Zebrafish possess tremendous intrinsic regenerative potential in ocular tissues, including the RPE, but little is known about the mechanisms that drive RPE regeneration. Here, utilizing zebrafish, we identified elements of the immune response as critical mediators of intrinsic RPE regeneration. Macrophages/microglia are responsive to RPE damage and are required for the timely progression of the regenerative response and our data highlight that inflammation post-RPE injury is also critical for normal RPE regeneration. These data are the first to identify the molecular and cellular underpinnings of RPE regeneration in any system and hold significant potential for translational approaches aimed towards promoting a pro-regenerative environment in mammals.

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mTOR activity is essential for retinal pigment epithelium regeneration in zebrafish

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Oxidative stress alters transcript localization of disease-causing genes in the retinal pigment epithelium

Project description:To evaluate the effect of oxidative stress on transcript localization in the retinal pigment epithelium (RPE), we performed poly-A RNA sequencing on nuclear and cytoplasmic fractions from induced pluripotent stem cell-derived retinal pigment epithelium (iPSC-RPE) cells exposed to hydrogen peroxide, as well as untreated 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.

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mTOR activity is essential for retinal pigment epithelium regeneration in zebrafish

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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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