Abstract
ABSTRACTUltraviolet (UV) radiation of eyes is a major risk factor for cataractogenesis, although the molecular mechanisms underlying this process remain poorly understood and genes that are affected by UV radiation have not been fully identified. In this study, we examined the UV-related gene regulation in lens epithelial cells (LECs) of mouse eyes and investigated the molecular mechanisms of UV-triggered cataractogenesis. Forty-one genes were significantly upregulated in LECs following UVB exposure in vivo in two independent experiments. Among these, Otx2 was strongly upregulated in LECs, suggesting that it may act as an upstream regulator of UVB-induced changes in gene expression. Accordingly, Otx2 overexpression in LECs in vitro induced morphological changes in cell shapes. Epithelial–mesenchymal transition (EMT)-related molecules, such as TGFβ2, αSMA and fibronectin were upregulated in Otx2-overexpressing LECs, concomitant with suppression of lens fiber cell marker genes, such as CRYAA and DNASEIIB. In vitro experiments suggested that UVB upregulated Otx2 through hydrogen peroxide generation. Aberrant upregulation of Otx2 in LECs following UV irradiation induces the EMT and alteration of the lens cell characteristics, likely contributing to cataractogenesis.
Highlights
Cataract is the cause of blindness in 33.4% of cases globally (Khairallah et al, 2015)
The ingenuity pathway analysis (IPA) software indicated that the homeobox protein Otx2 is an upstream regulatory transcription factor that is sensitive to UVB irradiation (P value of overlap=2.33 E-15; Predicted Activation State, Activated; Fig. 1D)
We show that UVB irradiation of eye lenses upregulates Otx2 in LECs and that Otx2 induced Epithelial–mesenchymal transition (EMT) in lens epithelial cells, resulting in alteration of lens cell characteristics
Summary
Cataract is the cause of blindness in 33.4% of cases globally (Khairallah et al, 2015). Previous epidemiological studies show that ultraviolet (UV) exposures of lenses are a major risk factor for cataractogenesis (Bochow et al, 1989). The ensuing molecular mechanisms and global transcriptional changes during UV-induced cataractogenesis remain unclear. Studies of the molecular mechanisms of cataractogenesis and the development of noninvasive prevention and treatment methods for cataractogenesis are eagerly awaited.
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