Pharmacologic fibroblast reprogramming into photoreceptors restores vision

Biraj Mahato, Koray Dogan Kaya, Yan Fan, Nathalie Sumien, Ritu A. Shetty, Wei Zhang, Delaney Davis, Thomas Mock, Subrata Batabyal, Aiguo Ni, Samarendra Mohanty, Zongchao Han, Rafal Farjo, Michael J. Forster, Anand Swaroop and Sai H. Chavala ()
Additional contact information
Biraj Mahato: University of North Texas Health Science Center
Koray Dogan Kaya: National Institutes of Health
Yan Fan: University of North Texas Health Science Center
Nathalie Sumien: University of North Texas Health Science Center
Ritu A. Shetty: University of North Texas Health Science Center
Wei Zhang: University of North Texas Health Science Center
Delaney Davis: University of North Texas Health Science Center
Thomas Mock: University of North Texas Health Science Center
Subrata Batabyal: Nanoscope Technologies LLC
Aiguo Ni: University of North Texas Health Science Center
Samarendra Mohanty: Nanoscope Technologies LLC
Zongchao Han: University of North Carolina at Chapel Hill
Rafal Farjo: EyeCRO LLC
Michael J. Forster: University of North Texas Health Science Center
Anand Swaroop: National Institutes of Health
Sai H. Chavala: University of North Texas Health Science Center

Nature, 2020, vol. 581, issue 7806, 83-88

Abstract: 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-κB and the upregulation of Ascl1. We anticipate that CiPCs could have therapeutic potential for restoring vision.

Date: 2020
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-020-2201-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:581:y:2020:i:7806:d:10.1038_s41586-020-2201-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-020-2201-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().