Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration.
Fructosamine-3-Kinase as a Potential Treatment Option for Age-Related Macular Degeneration.
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DOI：
10.3390/jcm9092869
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发表时间：
2020-09-04
影响因子：
3.9
通讯作者：
Delanghe JR
中科院分区：
文献类型：
--
作者：
De Bruyne S;Van den Broecke C;Vrielinck H;Khelifi S;De Wever O;Bracke K;Huizing M;Boston N;Himpe J;Speeckaert M;Vral A;Van Dorpe J;Van Aken E;Delanghe JR
视网膜黄斑变性是发达国家致盲的主要原因。由于晚期糖基化终产物（AGEs）通过各种证据与AMD的发病机制有关，我们研究了果糖胺-3-激酶（FN 3 K）在AMD患者视网膜AGEs、玻璃状物质和玻璃状病变中的破坏潜力。测量AGE型自体荧光以评估FN 3 K对甘糖醛酸酯诱导的AGE修饰的猪神经视网膜和未修饰的人神经视网膜的作用。对暴露于香烟烟雾和空气中的小鼠的成对眼睛进行处理和组织学评价。对人体组织切片进行自动光学图像分析，以比较对照和FN 3 K治疗的玻璃疣，并进行近红外（NIR）显微光谱分析，以检查生物化学差异。光学相干断层扫描（OCT）用于评估FN 3 K对死后人眼处理后的玻璃疣样沉积物的影响。FN 3 K处理引起AGE修饰的猪视网膜中AGE相关的自发荧光显著降低（41%）。此外，对人类神经视网膜的治疗导致自发荧光显着减少（-24%）。FN 3 K处理的小鼠眼睛显示出较少的玻璃状物质。组织切片上玻璃疣的成对比较揭示了FN 3 K治疗后颜色强度的显著变化。近红外显微光谱揭示了FN 3 K治疗后玻璃疣样物质（布鲁赫膜）和玻璃疣的清晰光谱差异。离体治疗强烈地减小了OCT成像上视网膜下玻璃疣样病变的尺寸（高达83%）。总之，我们的研究首次证明了FN 3 K在AMD患者中破坏AGE相关视网膜自发荧光、玻璃状物质和玻璃状病变中的潜在作用。
Age-related macular degeneration is the leading cause of blindness in the developed world. Since advanced glycation end products (AGEs) are implicated in the pathogenesis of AMD through various lines of evidence, we investigated the potential of fructosamine-3-kinase (FN3K) in the disruption of retinal AGEs, drusenoid material and drusenoid lesions in patients with AMD. AGE-type autofluorescence was measured to evaluate the effects of FN3K on glycolaldehyde-induced AGE-modified neural porcine retinas and unmodified human neural retinas. Eye pairs from cigarette-smoke- and air-exposed mice were treated and evaluated histologically. Automated optical image analysis of human tissue sections was performed to compare control- and FN3K-treated drusen and near-infrared (NIR) microspectroscopy was performed to examine biochemical differences. Optical coherence tomography (OCT) was used to evaluate the effect of FN3K on drusenoid deposits after treatment of post-mortem human eyes. FN3K treatment provoked a significant decrease (41%) of AGE-related autofluorescence in the AGE-modified porcine retinas. Furthermore, treatment of human neural retinas resulted in significant decreases of autofluorescence (−24%). FN3K-treated murine eyes showed less drusenoid material. Pairwise comparison of drusen on tissue sections revealed significant changes in color intensity after FN3K treatment. NIR microspectroscopy uncovered clear spectral differences in drusenoid material (Bruch’s membrane) and drusen after FN3K treatment. Ex vivo treatment strongly reduced size of subretinal drusenoid lesions on OCT imaging (up to 83%). In conclusion, our study demonstrated for the first time a potential role of FN3K in the disruption of AGE-related retinal autofluorescence, drusenoid material and drusenoid lesions in patients with AMD.
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影响因子：
7.7
作者：
Delpierre, G;Rider, MH;Van Schaftingen, E
通讯作者：
Van Schaftingen, E
影响因子：
10.3
作者：
De Bruyne, Sander;Speeckaert, R.;Delanghe, J.
通讯作者：
Delanghe, J.
影响因子：
4.4
作者：
Espinosa-Heidmann, DG;Suner, IJ;Cousins, SW
通讯作者：
Cousins, SW
DOI：
10.1073/pnas.222551899
发表时间：
2002-11-12
影响因子：
11.1
作者：
Crabb, JW;Miyagi, M;Hollyfield, JG
通讯作者：
Hollyfield, JG
影响因子：
4.4
作者：
Glenn, Josephine V.;Mahaffy, Helen;Stitt, Alan W.
通讯作者：
Stitt, Alan W.