Dataset Information

Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

ABSTRACT: Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision1,2. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod photoreceptor-like cells. The transplantation of these chemically induced photoreceptor-like cells (CiPCs) into the subretinal space of rod degeneration mice (homozygous for rd1, also known as Pde6b) leads to partial restoration of the pupil reflex and visual function. We show that mitonuclear communication is a key determining factor for the reprogramming of fibroblasts into CiPCs. Specifically, treatment with these five compounds leads to the translocation of AXIN2 to the mitochondria, which results in the production of reactive oxygen species, the activation of NF-?B and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.

SUBMITTER: Mahato B

PROVIDER: S-EPMC7469946 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

Mahato Biraj B Kaya Koray Dogan KD Fan Yan Y Sumien Nathalie N Shetty Ritu A RA Zhang Wei W Davis Delaney D Mock Thomas T Batabyal Subrata S Ni Aiguo A Mohanty Samarendra S Han Zongchao Z Farjo Rafal R Forster Michael J MJ Swaroop Anand A Chavala Sai H SH

Nature 20200415 7806

Photoreceptor loss is the final common endpoint in most retinopathies that lead to irreversible blindness, and there are no effective treatments to restore vision<sup>1,2</sup>. Chemical reprogramming of fibroblasts offers an opportunity to reverse vision loss; however, the generation of sensory neuronal subtypes such as photoreceptors remains a challenge. Here we report that the administration of a set of five small molecules can chemically induce the transformation of fibroblasts into rod phot ...[more]

PMID: 32376950

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Project description:Visual speech facilitates auditory speech perception, but the visual cues responsible for these benefits and the information they provide remain unclear. Low-level models emphasize basic temporal cues provided by mouth movements, but these impoverished signals may not fully account for the richness of auditory information provided by visual speech. High-level models posit interactions among abstract categorical (i.e., phonemes/visemes) or amodal (e.g., articulatory) speech representations, but require lossy remapping of speech signals onto abstracted representations. Because visible articulators shape the spectral content of speech, we hypothesized that the perceptual system might exploit natural correlations between midlevel visual (oral deformations) and auditory speech features (frequency modulations) to extract detailed spectrotemporal information from visual speech without employing high-level abstractions. Consistent with this hypothesis, we found that the time-frequency dynamics of oral resonances (formants) could be predicted with unexpectedly high precision from the changing shape of the mouth during speech. When isolated from other speech cues, speech-based shape deformations improved perceptual sensitivity for corresponding frequency modulations, suggesting that listeners could exploit this cross-modal correspondence to facilitate perception. To test whether this type of correspondence could improve speech comprehension, we selectively degraded the spectral or temporal dimensions of auditory sentence spectrograms to assess how well visual speech facilitated comprehension under each degradation condition. Visual speech produced drastically larger enhancements during spectral degradation, suggesting a condition-specific facilitation effect driven by cross-modal recovery of auditory speech spectra. The perceptual system may therefore use audiovisual correlations rooted in oral acoustics to extract detailed spectrotemporal information from visual speech.

Dataset Information

Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

Publications

Pharmacologic fibroblast reprogramming into photoreceptors restores vision.

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