TY - JOUR TI - Canonical NF-κB signaling maintains corneal epithelial integrity and prevents corneal aging via retinoic acid AU - Yu, Qian AU - Biswas, Soma AU - Ma, Gang AU - Zhao, Peiquan AU - Li, Baojie AU - Li, Jing A2 - Smith, Lois A2 - Cheah, Kathryn Song Eng VL - 10 PY - 2021 DA - 2021/06/04 SP - e67315 C1 - eLife 2021;10:e67315 DO - 10.7554/eLife.67315 UR - https://doi.org/10.7554/eLife.67315 AB - 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-κB 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; Relaf/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-κB-retinoic acid pathway as a therapeutic target for corneal disorders. KW - angiogenesis inhibitor KW - blindness KW - corneal disorders KW - NF-κB KW - retinoic acid JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -