| First Author | Yu Q | Year | 2021 |
| Journal | Elife | Volume | 10 |
| PubMed ID | 34085926 | Mgi Jnum | J:317349 |
| Mgi Id | MGI:6727612 | Doi | 10.7554/eLife.67315 |
| Citation | Yu Q, et al. (2021) Canonical NF-kappaB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid. Elife 10:e67315 |
| abstractText | Disorders of the transparent cornea affect millions of people worldwide. However, how to maintain and/or regenerate this organ remains unclear. Here, we show that Rela (encoding a canonical NF-kappaB subunit) ablation in K14(+) corneal epithelial stem cells not only disrupts corneal regeneration but also results in age-dependent epithelial deterioration, which triggers aberrant wound-healing processes including stromal remodeling, neovascularization, epithelial metaplasia, and plaque formation at the central cornea. These anomalies are largely recapitulated in normal mice that age naturally. Mechanistically, Rela deletion suppresses expression of Aldh1a1, an enzyme required for retinoic acid synthesis from vitamin A. Retinoic acid administration blocks development of ocular anomalies in Krt14-Cre; Rela(f/f) mice and naturally aged mice. Moreover, epithelial metaplasia and plaque formation are preventable by inhibition of angiogenesis. This study thus uncovers the major mechanisms governing corneal maintenance, regeneration, and aging and identifies the NF-kappaB-retinoic acid pathway as a therapeutic target for corneal disorders. |
