Reprogramming to recover youthful epigenetic information and restore vision
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PROVIDER: PRJNA614634 | ENA |
REPOSITORIES: ENA
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Project description:Reprogramming to recover youthful epigenetic information and restore vision
| PRJNA655981 | ENA
Project description:Epigenetic reprogramming via a combination of three Yamanaka factors, Oct4, Sox2, and Klf4 (OSK), provides an effective way to promote axon regeneration in chemical- or injury-damaged neurons and improve neuronal function in aged mice. DNA methylation landscape is remodeled during this reprogramming process. This study was designed to examine DNA methylation age in differentiated human neurons post axonal damage with or without OSK expression. Differentiated SH-SY5Y neurons were transduced with AAV.DJ vectors to induce OSK expression for five days, followed by 24-hr treatment with 100nM vincristine (VCS) to induce neurite degeneration. Neurons were harvested at either day 1 or day 9 after VCS treatment. The Illumina Infinium DNA methylation EPIC array was used to obtain DNA methylation profiles. The skin & blood clock from Horvath 2018 (PMID: 30048243 PMCID: PMC6075434) was used for DNA methylation age analysis.
2020-09-26 | GSE147436 | GEO
Project description:Ageing is a degenerative process that leads to tissue dysfunction and death. A proposed cause of ageing is the accumulation of epigenetic noise that disrupts gene expression patterns, leading to decreases in tissue function and regenerative capacity1-3. Changes to DNA methylation patterns over time form the basis of ageing clocks4, but whether older individuals retain the information needed to restore these patterns-and, if so, whether this could improve tissue function-is not known. Over time, the central nervous system (CNS) loses function and regenerative capacity5-7. Using the eye as a model CNS tissue, here we show that ectopic expression of Oct4 (also known as Pou5f1), Sox2 and Klf4 genes (OSK) in mouse retinal ganglion cells restores youthful DNA methylation patterns and transcriptomes, promotes axon regeneration after injury, and reverses vision loss in a mouse model of glaucoma and in aged mice. The beneficial effects of OSK-induced reprogramming in axon regeneration and vision require the DNA demethylases TET1 and TET2. These data indicate that mammalian tissues retain a record of youthful epigenetic information-encoded in part by DNA methylation-that can be accessed to improve tissue function and promote regeneration in vivo.
| S-EPMC7752134 | biostudies-literature
Project description:Rod-cone dystrophy (RCD), or retinitis pigmentosa, involves genetic conditions where rod degeneration precedes cone degeneration, resulting in tunnel vision and eventual blindness. Previous studies attempted to restore cone activity and prolong vision by expressing microbial chloride pumps in degenerating cone photoreceptors. However, microbial opsins require high expression and intense light, limiting their effectiveness. In this work, we explored the phototransduction cascade in degenerating cones in two RCD mouse models. We observed that opsin and arrestin expression persists in the soma during outer segment degeneration. This led us to hypothesize that reactivating cones based on cone opsin signaling may be possible by expressing a target channel activated by G proteins recruited by cone opsin. Through adeno-associated viral (AAV) mediated expression of the G protein-coupled inwardly rectifying K (GIRK) channel, we achieved improvements in visual function in two RCD mouse models with mutations in different genes. Importantly, we validated the rationale of GIRK-mediated gene therapy in humans by confirming cone opsin and cone arrestin expression in cones of late-stage RCD patients. Our proposed approach involves GIRK channel expression in cones as a novel method to maintain high acuity, sensitivity, and color vision in RCD, independent of the underlying mutation.
2025-01-13 | GSE286529 | GEO
Project description:Composting biotechnology information Genome sequencing
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Project description:Retinal Contributions to Vision Loss in Albinism
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Project description:The restoration of light response with complex spatiotemporal features in retinal degenerative diseases towards retinal prosthesis has proven to be a considerable challenge over the past decades. Herein, inspired by the structure and function of photoreceptors in retinas, we develop artificial photoreceptors based on gold nanoparticle-decorated titania nanowire arrays, for restoration of visual responses in the blind mice with degenerated photoreceptors. Green, blue and near UV light responses in the retinal ganglion cells (RGCs) are restored with a spatial resolution better than 100 µm. ON responses in RGCs are blocked by glutamatergic antagonists, suggesting functional preservation of the remaining retinal circuits. Moreover, neurons in the primary visual cortex respond to light after subretinal implant of nanowire arrays. Improvement in pupillary light reflex suggests the behavioral recovery of light sensitivity. Our study will shed light on the development of a new generation of optoelectronic toolkits for subretinal prosthetic devices.
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