Kesper Christiane, Viestenz Arne, Wiese-Rischke Cornelia, Scheller Marina, Hammer Thomas
Department of Ophthalmology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, D-06120, Halle (Saale), Germany.
Department of Ophthalmology, University Hospital Halle (Saale), Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Straße 40, D-06120, Halle (Saale), Germany.
Exp Eye Res. 2022 May;218:108985. doi: 10.1016/j.exer.2022.108985. Epub 2022 Feb 25.
The limbus of the eye is the location of the corneal epithelial stem cell niche. These cells are necessary for continuous renewal of the corneal epithelium. In the case of limbal stem cell deficiency, these cells are damaged, and the whole cornea becomes opaque. It is important to be able to identify stem cells that could be applied for new therapeutic strategies. There are various known markers to characterize these cells, including p63, Nanog, oct4 and FGFR2. However, none of these markers are exclusively expressed in these stem cells (they are also expressed in transient amplified cells). It seems likely that a combination of stem cell markers will be necessary for corneal stem cell identification. The aim of this study was to detect IRF8 in limbal epithelial stem cells and to determine its function. In a mouse model, IRF8 could be detected in limbal and basal epithelial cells of the cornea by histological and immunohistological staining of wild-type mouse eyes. Furthermore, the limbus of the eye was significantly smaller in IRF8-knockout mice than in wild-type mice, and the expression of Nanog was lower in IRF8-knockout mice. This suggests that IRF8 has an influence on the maintenance of stem cell properties in the limbus, possibly by affecting the expression of Nanog. Furthermore, IRF8 has an impact on E-cadherin and N-cadherin expression in the mouse eye.
眼角膜缘是角膜上皮干细胞龛的所在位置。这些细胞对于角膜上皮的持续更新至关重要。在角膜缘干细胞缺乏的情况下，这些细胞会受损，整个角膜会变得混浊。能够识别可应用于新治疗策略的干细胞很重要。有多种已知的标志物可用于表征这些细胞，包括p63、Nanog、oct4和FGFR2。然而，这些标志物均未在这些干细胞中特异性表达（它们也在短暂扩增细胞中表达）。角膜干细胞的识别可能需要干细胞标志物的组合。本研究的目的是检测眼角膜缘上皮干细胞中的IRF8并确定其功能。在小鼠模型中，通过对野生型小鼠眼睛进行组织学和免疫组织化学染色，可在角膜的角膜缘和基底上皮细胞中检测到IRF8。此外，IRF8基因敲除小鼠的眼角膜缘明显小于野生型小鼠，且IRF8基因敲除小鼠中Nanog的表达较低。这表明IRF8可能通过影响Nanog的表达对角膜缘干细胞特性的维持产生影响。此外，IRF8对小鼠眼中E-钙黏蛋白和N-钙黏蛋白的表达有影响。
