Department of Diagnostic Sciences, Ghent University, 9000 Ghent, Belgium.
Department of Green Chemistry and Technology, MSsmall Expertise Centre, Mass Spectrometry Analysis of Small Organic Molecules, Ghent University, 9000 Ghent, Belgium.
Int J Mol Sci. 2024 Apr 27;25(9):4779. doi: 10.3390/ijms25094779.
Age-related macular degeneration (AMD) is an age-related disorder that is a global public health problem. The non-enzymatic Maillard reaction results in the formation of advanced glycation end products (AGEs). Accumulation of AGEs in drusen plays a key role in AMD. AGE-reducing drugs may contribute to the prevention and treatment of AGE-related disease. Fructosamine oxidase (FAOD) acts on fructosyl lysine and fructosyl valine. Based upon the published results of fructosamine 3-kinase (FN3K) and FAOD obtained in cataract and presbyopia, we studied ex vivo FAOD treatment as a non-invasive AMD therapy. On glycolaldehyde-treated porcine retinas, FAOD significantly reduced AGE autofluorescence ( = 0.001). FAOD treatment results in a breakdown of AGEs, as evidenced using UV fluorescence, near-infrared microspectroscopy on stained tissue sections of human retina, and gel permeation chromatography. Drusen are accumulations of AGEs that build up between Bruch's membrane and the retinal pigment epithelium. On microscopy slides of human retina affected by AMD, a significant reduction in drusen surface to 45 ± 21% was observed following FAOD treatment. Enzymatic digestion followed by mass spectrometry of fructose- and glucose-based AGEs (produced in vitro) revealed a broader spectrum of substrates for FAOD, as compared to FN3K, including the following: fructosyllysine, carboxymethyllysine, carboxyethyllysine, and imidazolone. In contrast to FN3K digestion, agmatine (4-aminobutyl-guanidine) was formed following FAOD treatment in vitro. The present study highlights the therapeutic potential of FAOD in AMD by repairing glycation-induced damage.
年龄相关性黄斑变性（AMD）是一种与年龄相关的疾病，也是一个全球性的公共健康问题。非酶糖基化反应导致晚期糖基化终产物（AGEs）的形成。在 AMD 中，沉积物中 AGEs 的积累起着关键作用。减少 AGEs 的药物可能有助于预防和治疗与 AGE 相关的疾病。果糖胺氧化酶（FAOD）作用于果糖基赖氨酸和果糖基缬氨酸。基于已发表的在白内障和老花眼中的果糖胺 3-激酶（FN3K）和 FAOD 的结果，我们研究了 FAOD 治疗作为一种非侵入性 AMD 治疗方法的效果。在甘醛处理的猪视网膜上，FAOD 显著降低了 AGE 自发荧光（=0.001）。FAOD 治疗导致 AGE 分解，这在使用 UV 荧光、经染色的人视网膜组织切片的近红外微光谱学和凝胶渗透色谱法检测中得到了证实。沉积物是在布鲁赫膜和视网膜色素上皮之间积聚的 AGEs。在受 AMD 影响的人视网膜显微镜载玻片上，FAOD 处理后观察到沉积物表面减少了 45±21%。对体外产生的果糖和葡萄糖基 AGEs（果糖基赖氨酸、羧甲基赖氨酸、羧乙基赖氨酸和咪唑烷酮）进行酶促消化和质谱分析后发现，FAOD 的底物谱比 FN3K 更广泛，包括以下几种：。与 FN3K 消化不同，FAOD 处理体外形成胍丁胺（4-氨基丁基-胍）。本研究通过修复糖化诱导的损伤，强调了 FAOD 在 AMD 中的治疗潜力。
