Aberrant TGF-β1 signaling activation by MAF underlies pathological lens growth in high myopia.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33833231.
- Also identified by DOI 10.1038/s41467-021-22041-2 and PMC identifier 8032689.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
High myopia is a leading cause of blindness worldwide. Myopia progression may lead to pathological changes of lens and affect the outcome of lens surgery, but the underlying mechanism remains unclear. Here, we find an increased lens size in highly myopic eyes associated with up-regulation of β/γ-crystallin expressions. Similar findings are replicated in two independent mouse models of high myopia. Mechanistic studies show that the transcription factor MAF plays an essential role in up-regulating β/γ-crystallins in high myopia, by direct activation of the crystallin gene promoters and by activation of TGF-β1-Smad signaling. Our results establish lens morphological and molecular changes as a characteristic feature of high myopia, and point to the dysregulation of the MAF-TGF-β1-crystallin axis as an underlying mechanism, providing an insight for therapeutic interventions.
Medical subject headings
- Lens, Crystalline
- Maf Transcription Factors
- Myopia, Degenerative
- Transforming Growth Factor beta1
- beta-Crystallins
- gamma-Crystallins