McKay Tina B, Kivanany Pouriska B, Nicholas Sarah E, Nag Okhil K, Elliott Michael H, Petroll W Matthew, Karamichos Dimitrios
Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Metabolites. 2022 Jul 7;12(7):626. doi: 10.3390/metabo12070626.
We have previously reported the flavonoid, quercetin, as a metabolic regulator and inhibitor of myofibroblast differentiation in vitro. Our current study evaluated the effects of topical application of quercetin on corneal scar development using two different animal models followed by RNA analysis in vitro. Wild-type C57BL/6J mice were anesthetized and the corneal epithelium and stroma were manually debrided, followed by quercetin (0.5, 1, 5, or 50 mM) or vehicle application. Corneal scarring was assessed for 3 weeks by slit lamp imaging and clinically scored. In a separate animal study, six New Zealand White rabbits underwent lamellar keratectomy surgery, followed by treatment with 5 mM quercetin or vehicle twice daily for three days. Stromal backscattering was assessed at week 3 by in vivo confocal microscopy. In mice, a single dose of 5 mM quercetin reduced corneal scar formation. In rabbits, stromal backscattering was substantially lower in two out of three animals in the quercetin-treated group. In vitro studies of human corneal fibroblasts showed that quercetin modulated select factors of the transforming growth factor-β (TGF-β) signaling pathway. These results provide evidence that quercetin may inhibit corneal scarring. Further studies in a larger cohort are required to validate the efficacy and safety of quercetin for clinical applications.
我们之前曾报道过黄酮类化合物槲皮素,它在体外是一种代谢调节剂和肌成纤维细胞分化抑制剂。我们目前的研究使用两种不同的动物模型评估了局部应用槲皮素对角膜瘢痕形成的影响,随后进行了体外RNA分析。将野生型C57BL/6J小鼠麻醉,手动刮除角膜上皮和基质,然后应用槲皮素(0.5、1、5或50 mM)或赋形剂。通过裂隙灯成像评估角膜瘢痕形成3周,并进行临床评分。在另一项动物研究中,六只新西兰白兔接受了板层角膜切除术,然后每天两次用5 mM槲皮素或赋形剂治疗三天。在第3周通过体内共聚焦显微镜评估基质后向散射。在小鼠中,单剂量5 mM槲皮素可减少角膜瘢痕形成。在兔子中,槲皮素治疗组三只动物中有两只的基质后向散射明显较低。对人角膜成纤维细胞的体外研究表明,槲皮素可调节转化生长因子-β(TGF-β)信号通路的特定因子。这些结果提供了证据表明槲皮素可能抑制角膜瘢痕形成。需要在更大的队列中进行进一步研究以验证槲皮素临床应用的有效性和安全性。