Fluorescence Lifetime Imaging of Human Sub-RPE Calcification In Vitro Following Chlortetracycline Infusion.
Fluorescence Lifetime Imaging of Human Sub-RPE Calcification In Vitro Following Chlortetracycline Infusion.
复制标题
DOI：
10.3390/ijms24076421
复制
发表时间：
2023-03-29
影响因子：
5.6
通讯作者：
Thompson, Richard B.
中科院分区：
文献类型：
--
作者：
Hegde, Kavita R.;Puche, Adam C.;Szmacinski, Henryk;Fuller, Kristina;Ray, Krishanu;Patel, Nikita;Lengyel, Imre;Thompson, Richard B.
关键词：
我们已经证明，所有检查的视网膜下色素上皮（sub-RPE）沉积物都含有磷酸钙矿物质：羟基磷灰石（HAP）、白磷钙石（Wht）或两者兼而有之。这些通常采用CA的形式。1 μm直径的小球或>10 μm的结节，似乎参与年龄相关性黄斑变性（AMD）的发展和进展。因此，这些矿物质可以作为有用的生物标志物，用于早期检测和监测AMD中的亚RPE变化。我们证明，HAP存款可以在体外成像的荧光寿命成像显微镜（FLIM）在平板安装的视网膜使用传统的四环素抗生素作为HAP的选择性传感器。由于FLIM图像上的对比度是基于荧光寿命的差异而不是四环素染色HAP的强度，因此显着提高了组织自发荧光与背景的区分。本初步研究的重点是评估是否血管灌注的耐受性良好和特点的金霉素（广泛用作口服生物利用度的抗生素）可以荧光标记视网膜HAP使用人尸体。我们发现，通过外周循环递送的四环素确实可以选择性地标记亚RPE沉积物，从而打开了其用于眼科监测一系列疾病的可能性，在这些疾病中报告了存款形成，例如AMD和阿尔茨海默病（AD）。
We have shown that all sub-retinal pigment epithelial (sub-RPE) deposits examined contain calcium phosphate minerals: hydroxyapatite (HAP), whitlockite (Wht), or both. These typically take the form of ca. 1 μm diameter spherules or >10 μm nodules and appear to be involved in the development and progression of age-related macular degeneration (AMD). Thus, these minerals may serve as useful biomarkers the for early detection and monitoring of sub-RPE changes in AMD. We demonstrated that HAP deposits could be imaged in vitro by fluorescence lifetime imaging microscopy (FLIM) in flat-mounted retinas using legacy tetracycline antibiotics as selective sensors for HAP. As the contrast on a FLIM image is based on the difference in fluorescence lifetime and not intensity of the tetracycline-stained HAP, distinguishing tissue autofluorescence from the background is significantly improved. The focus of the present pilot study was to assess whether vascular perfusion of the well tolerated and characterized chlortetracycline (widely used as an orally bioavailable antibiotic) can fluorescently label retinal HAP using human cadavers. We found that the tetracycline delivered through the peripheral circulation can indeed selectively label sub-RPE deposits opening the possibility for its use for ophthalmic monitoring of a range of diseases in which deposit formation is reported, such as AMD and Alzheimer disease (AD).
登录
查看更多内容
影响因子：
17.8
作者：
Dysli C;Wolf S;Berezin MY;Sauer L;Hammer M;Zinkernagel MS
通讯作者：
Zinkernagel MS
DOI：
10.1002/dad2.12232
发表时间：
2021
期刊：
Alzheimer's & dementia (Amsterdam, Netherlands)
影响因子：
--
作者：
Csincsik L;Quinn N;Yong KXX;Crutch SJ;Peto T;Lengyel I
通讯作者：
Lengyel I
影响因子：
2.1
作者：
Csincsik, Lajos;MacGillivray, Thomas J.;Lengyel, Imre
通讯作者：
Lengyel, Imre
影响因子：
--
作者：
Pilgrim, Matthew G.;Marouf, Salma;Fearn, Sarah;Csincsik, Lajos;Kortvely, Elod;Knowles, Jonathan C.;Malek, Goldis;Thompson, Richard B.;Lengyel, Imre
通讯作者：
Lengyel, Imre
影响因子：
9.7
作者：
Tsolaki, Elena;Csincsik, Lajos;Bertazzo, Sergio
通讯作者：
Bertazzo, Sergio