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.
journal_name
Naturejournal_title
Natureauthors
Mahato B,Kaya KD,Fan Y,Sumien N,Shetty RA,Zhang W,Davis D,Mock T,Batabyal S,Ni A,Mohanty S,Han Z,Farjo R,Forster MJ,Swaroop A,Chavala SHdoi
10.1038/s41586-020-2201-4subject
Has Abstractpub_date
2020-05-01 00:00:00pages
83-88issue
7806eissn
0028-0836issn
1476-4687pii
10.1038/s41586-020-2201-4journal_volume
581pub_type
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