In vivo longitudinal 920 nm two-photon intravital kidney imaging of a dynamic 2,8-DHA crystal formation and tubular deterioration in the adenine-induced chronic kidney disease mouse model
In vivo longitudinal 920 nm two-photon intravital kidney imaging of a dynamic 2,8-DHA crystal formation and tubular deterioration in the adenine-induced chronic kidney disease mouse model
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DOI：
10.1364/boe.485187
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发表时间：
2023-04-01
影响因子：
3.4
通讯作者：
Kim, Pilhan
中科院分区：
文献类型：
--
作者：
Choi, Jieun;Choi, Min -sun;Kim, Pilhan
慢性肾脏疾病（Chronic kidney disease， CKD）是最常见的肾脏疾病之一，表现为肾功能逐渐丧失，早期无症状。包括高血压、糖尿病、高胆固醇和肾脏感染等多种病因的CKD发病机制尚不清楚。CKD动物模型肾脏的体内纵向重复细胞水平观察可以通过可视化CKD随时间进展的动态变化的病理生理，为CKD的诊断和治疗提供新的见解。本研究采用920 nm固定波长fs脉冲激光双光子活体显微镜，对腺嘌呤饮食诱导的CKD小鼠模型肾脏进行了30天的纵向和重复观察。有趣的是，我们可以利用二次谐波产生（SHG）信号成功地观察到2,8-二羟基腺嘌呤（2,8- dha）晶体的形成，并利用单920 nm双光子激发的自体荧光观察到肾小管的形态恶化。纵向体内双光子成像结果显示，SHG和自身荧光信号分别显示2,8- dha晶体增加和管状面积比减少，这与血液检测监测的CKD进展高度相关，血液检测显示随着时间的推移，胱抑素C和血尿素氮（BUN）水平升高。这一结果表明，无标记二次谐波晶体成像作为一种新的光学技术在体内CKD进展监测的潜力。(c) 2023年Optica出版集团根据Optica开放获取出版协议的条款
Chronic kidney disease (CKD) is one of the most common renal diseases manifested by gradual loss of kidney function with no symptoms in the early stage. The underlying mechanism in the pathogenesis of CKD with various causes such as high blood pressure, diabetes, high cholesterol, and kidney infection is not well understood. In vivo longitudinal repetitive cellular-level observation of the kidney of the CKD animal model can provide novel insights to diagnose and treat the CKD by visualizing the dynamically changing pathophysiology of CKD with its progression over time. In this study, using two-photon intravital microscopy with a single 920 nm fixed-wavelength fs-pulsed laser, we longitudinally and repetitively observed the kidney of an adenine diet-induced CKD mouse model for 30 days. Interestingly, we could successfully visualize the 2,8-dihydroxyadenine (2,8-DHA) crystal formation with a second-harmonics generation (SHG) signal and the morphological deterioration of renal tubules with autofluorescence using a single 920 nm two-photon excitation. The longitudinal in vivo two-photon imaging results of increasing 2,8-DHA crystals and decreasing tubular area ratio visualized by SHG and autofluorescence signal, respectively, were highly correlated with the CKD progression monitored by a blood test showing increased cystatin C and blood urea nitrogen (BUN) levels over time. This result suggests the potential of label-free second-harmonics generation crystal imaging as a novel optical technique for in vivo CKD progression monitoring. (c) 2023 Optica Publishing Group under the terms of the Optica Open Access Publishing Agreement