2/28/2023 0 Comments Integrity plus dewey![]() The cornea contributes 65–75% of the eye’s total focusing power and provides a barrier to protect against environmental insults ( Yazdanpanah et al., 2017). Corneal transparency is attributable to the lack of keratin secretion by epithelial cells, the specific arrangement of stromal lamellae, expression of crystallins by keratocytes, and the lack of vasculature ( Nowell and Radtke, 2017 Jester, 2008 Yam et al., 2020). While the epithelial layer undergoes constant turnover driven by corneal epithelial stem cells (CESCs), the stromal and endothelial layers are relatively quiescent in adults ( Castro-Muñozledo, 2013 Majo et al., 2008 Schlötzer-Schrehardt and Kruse, 2005). ![]() The cornea is a transparent organ composed of the epithelial, stromal, and endothelial layers ( Yazdanpanah et al., 2017 Nowell and Radtke, 2017 Collinson et al., 2004), with the epithelial basement membrane separating the epithelial and the stroma layers and the Descemet’s basement membrane separating the stroma and endothelial layers ( Wilson, 2020 Medeiros et al., 2018). 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. ![]() Moreover, epithelial metaplasia and plaque formation are preventable by inhibition of angiogenesis. Retinoic acid administration blocks development of ocular anomalies in Krt14-Cre Rela f/f mice and naturally aged mice. Mechanistically, Rela deletion suppresses expression of Aldh1a1, an enzyme required for retinoic acid synthesis from vitamin A. These anomalies are largely recapitulated in normal mice that age naturally. 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. However, how to maintain and/or regenerate this organ remains unclear. Disorders of the transparent cornea affect millions of people worldwide.
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