Araya Umetsu , Masato Furuhashi , Megumi Watanabe , Ei Ohkawa , Yuri Tsugeno , Soma Suzuki , Kaku Itoh , Yosuke Ida , Fumihito Hikage , Hiroshi Ohguro
{"title":"脂肪酸代谢既参与视网膜生理,也参与视网膜血管疾病的病理","authors":"Araya Umetsu , Masato Furuhashi , Megumi Watanabe , Ei Ohkawa , Yuri Tsugeno , Soma Suzuki , Kaku Itoh , Yosuke Ida , Fumihito Hikage , Hiroshi Ohguro","doi":"10.1016/j.plefa.2022.102473","DOIUrl":null,"url":null,"abstract":"<div><p>To study the pathophysiological roles of the fatty acid-binding proteins (FABPs) within the retina, we performed; (1) immunolabeling of human retinas, wild type (WT) rat and mouse retinas, rat models for diabetic retinopathy (DR) and retinitis pigmentosa (RP) with anti-FABP3, FABP4, FABP5, FABP7, FABP8 and FABP12, (2) electroretinogram (ERG) measurements of WT and FABP4-deficient (<em>Fabp4</em><sup>-/-</sup>) mice, (3) ELISA or gas chromatography measurements of plasma (P-) and vitreous (V-) levels of FABP4 and vascular endothelial growth factor A (VEGFA), and fatty acids (FAs) from patients with retinal vascular disease (RVD) including proliferative DR (PDR, <em>n</em> = 30) and retinal vein occlusion (RVO, <em>n</em> = 18) and non-RVD (<em>n</em> = 18). Within the human retina, diverse expressions of FABP3, FABP4, FABP7 and FABP8 were identified. In contrast, positive immunoreactivities toward only FABP4 and FABP12 were detected in the cases of rat and mouse retinas, and interestingly, the FABP4 labeling patterns for the WT, DR and RP rat retinas were different. The ERG amplitudes of <em>Fabp4</em><sup>-/-</sup> mice were enhanced compared with those of WT mice. The concentrations of V-FABP4, V-VEGFA and total FAs were significantly higher in RVD patients than in non-PDR patients (<em>P</em> < 0.05). The V-FAs levels of each were significantly and positively correlated with V-FABP4 and V-VEGFA, although no significant correlation between vitreous (V-) and plasma (P-) FABP4, VEGFA and FAs were detected. The current study reveals that V-FAs appear to have significant roles in both retinal physiology as well as the pathogenesis of RVD with FABP4, which is commonly expressed within the retina in most species.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"183 ","pages":"Article 102473"},"PeriodicalIF":3.0000,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0952327822000850/pdfft?md5=2f201f56344347c5125b2a835db34f64&pid=1-s2.0-S0952327822000850-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Fatty acid metabolism is involved in both retinal physiology and the pathology of retinal vascular diseases\",\"authors\":\"Araya Umetsu , Masato Furuhashi , Megumi Watanabe , Ei Ohkawa , Yuri Tsugeno , Soma Suzuki , Kaku Itoh , Yosuke Ida , Fumihito Hikage , Hiroshi Ohguro\",\"doi\":\"10.1016/j.plefa.2022.102473\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>To study the pathophysiological roles of the fatty acid-binding proteins (FABPs) within the retina, we performed; (1) immunolabeling of human retinas, wild type (WT) rat and mouse retinas, rat models for diabetic retinopathy (DR) and retinitis pigmentosa (RP) with anti-FABP3, FABP4, FABP5, FABP7, FABP8 and FABP12, (2) electroretinogram (ERG) measurements of WT and FABP4-deficient (<em>Fabp4</em><sup>-/-</sup>) mice, (3) ELISA or gas chromatography measurements of plasma (P-) and vitreous (V-) levels of FABP4 and vascular endothelial growth factor A (VEGFA), and fatty acids (FAs) from patients with retinal vascular disease (RVD) including proliferative DR (PDR, <em>n</em> = 30) and retinal vein occlusion (RVO, <em>n</em> = 18) and non-RVD (<em>n</em> = 18). Within the human retina, diverse expressions of FABP3, FABP4, FABP7 and FABP8 were identified. In contrast, positive immunoreactivities toward only FABP4 and FABP12 were detected in the cases of rat and mouse retinas, and interestingly, the FABP4 labeling patterns for the WT, DR and RP rat retinas were different. The ERG amplitudes of <em>Fabp4</em><sup>-/-</sup> mice were enhanced compared with those of WT mice. The concentrations of V-FABP4, V-VEGFA and total FAs were significantly higher in RVD patients than in non-PDR patients (<em>P</em> < 0.05). The V-FAs levels of each were significantly and positively correlated with V-FABP4 and V-VEGFA, although no significant correlation between vitreous (V-) and plasma (P-) FABP4, VEGFA and FAs were detected. 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引用次数: 0
摘要
为了研究脂肪酸结合蛋白(FABPs)在视网膜中的病理生理作用,我们进行了;(1)用抗fabp3、FABP4、FABP5、FABP7、FABP8和FABP12对人视网膜、野生型(WT)大鼠和小鼠视网膜、糖尿病视网膜病变(DR)和视网膜色素变性(RP)大鼠模型进行免疫标记,(2)对WT和FABP4缺陷(FABP4- /-)小鼠的视网膜电图(ERG)测定,(3)ELISA或气相色谱法测定血浆(P-)和玻璃体(V-)中FABP4和血管内皮生长因子A (VEGFA)的水平,和脂肪酸(FAs)来自视网膜血管疾病(RVD)患者,包括增殖性DR (PDR, n = 30)、视网膜静脉闭塞(RVO, n = 18)和非RVD (n = 18)。在人视网膜中,发现了FABP3、FABP4、FABP7和FABP8的不同表达。相比之下,在大鼠和小鼠视网膜中仅检测到对FABP4和FABP12的阳性免疫反应,有趣的是,WT、DR和RP大鼠视网膜的FABP4标记模式不同。与WT小鼠相比,Fabp4-/-小鼠的ERG振幅增强。RVD患者的V-FABP4、V-VEGFA和总FAs浓度显著高于非pdr患者(P <0.05)。玻璃体(V-)和血浆(P-) FABP4、VEGFA、FAs水平与V-FABP4和V-VEGFA水平无显著相关性,但各组织中V-FAs水平与V-FABP4、VEGFA和FAs水平均呈显著正相关。目前的研究表明,V-FAs似乎在视网膜生理和FABP4的RVD发病机制中都有重要作用,FABP4在大多数物种的视网膜中普遍表达。
Fatty acid metabolism is involved in both retinal physiology and the pathology of retinal vascular diseases
To study the pathophysiological roles of the fatty acid-binding proteins (FABPs) within the retina, we performed; (1) immunolabeling of human retinas, wild type (WT) rat and mouse retinas, rat models for diabetic retinopathy (DR) and retinitis pigmentosa (RP) with anti-FABP3, FABP4, FABP5, FABP7, FABP8 and FABP12, (2) electroretinogram (ERG) measurements of WT and FABP4-deficient (Fabp4-/-) mice, (3) ELISA or gas chromatography measurements of plasma (P-) and vitreous (V-) levels of FABP4 and vascular endothelial growth factor A (VEGFA), and fatty acids (FAs) from patients with retinal vascular disease (RVD) including proliferative DR (PDR, n = 30) and retinal vein occlusion (RVO, n = 18) and non-RVD (n = 18). Within the human retina, diverse expressions of FABP3, FABP4, FABP7 and FABP8 were identified. In contrast, positive immunoreactivities toward only FABP4 and FABP12 were detected in the cases of rat and mouse retinas, and interestingly, the FABP4 labeling patterns for the WT, DR and RP rat retinas were different. The ERG amplitudes of Fabp4-/- mice were enhanced compared with those of WT mice. The concentrations of V-FABP4, V-VEGFA and total FAs were significantly higher in RVD patients than in non-PDR patients (P < 0.05). The V-FAs levels of each were significantly and positively correlated with V-FABP4 and V-VEGFA, although no significant correlation between vitreous (V-) and plasma (P-) FABP4, VEGFA and FAs were detected. The current study reveals that V-FAs appear to have significant roles in both retinal physiology as well as the pathogenesis of RVD with FABP4, which is commonly expressed within the retina in most species.