Bower Andrew J, Arp Zane, Zhao Youbo, Li Joanne, Chaney Eric J, Marjanovic Marina, Hughes-Earle Angela, Boppart Stephen A
Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Department of Electrical and Computer Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
Exp Dermatol. 2016 May;25(5):362-7. doi: 10.1111/exd.12932. Epub 2016 Feb 13.
Topical steroids are known for their anti-inflammatory properties and are commonly prescribed to treat many adverse skin conditions such as eczema and psoriasis. While these treatments are known to be effective, adverse effects including skin atrophy are common. In this study, the progression of these effects is investigated in an in vivo mouse model using multimodal optical microscopy. Utilizing a system capable of performing two-photon excitation fluorescence microscopy (TPEF) of reduced nicotinamide adenine dinucleotide (NADH) to visualize the epidermal cell layers and second harmonic generation (SHG) microscopy to identify collagen in the dermis, these processes can be studied at the cellular level. Fluorescence lifetime imaging microscopy (FLIM) is also utilized to image intracellular NADH levels to obtain molecular information regarding metabolic activity following steroid treatment. In this study, fluticasone propionate (FP)-treated, mometasone furoate (MF)-treated and untreated animals were imaged longitudinally using a custom-built multimodal optical microscope. Prolonged steroid treatment over the course of 21 days is shown to result in a significant increase in mean fluorescence lifetime of NADH, suggesting a faster rate of maturation of epidermal keratinocytes. Alterations to collagen organization and the structural microenvironment are also observed. These results give insight into the structural and biochemical processes of skin atrophy associated with prolonged steroid treatment.
局部用类固醇因其抗炎特性而闻名,常用于治疗多种不良皮肤状况,如湿疹和牛皮癣。虽然这些治疗方法已知有效,但包括皮肤萎缩在内的不良反应很常见。在本研究中,使用多模态光学显微镜在体内小鼠模型中研究了这些影响的进展情况。利用能够对还原型烟酰胺腺嘌呤二核苷酸(NADH)进行双光子激发荧光显微镜(TPEF)以可视化表皮细胞层,以及利用二次谐波产生(SHG)显微镜来识别真皮中的胶原蛋白的系统,可以在细胞水平上研究这些过程。荧光寿命成像显微镜(FLIM)也用于对细胞内NADH水平进行成像,以获取有关类固醇治疗后代谢活性的分子信息。在本研究中,使用定制的多模态光学显微镜对接受丙酸氟替卡松(FP)治疗、糠酸莫米松(MF)治疗和未治疗的动物进行纵向成像。结果显示,在21天的过程中进行长期类固醇治疗会导致NADH的平均荧光寿命显著增加,这表明表皮角质形成细胞的成熟速度更快。还观察到胶原蛋白组织和结构微环境的改变。这些结果深入了解了与长期类固醇治疗相关的皮肤萎缩的结构和生化过程。