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Role of biometals in activation of immune cum inflammatory response in ovine ageing eye: a potential model for understanding human geriatric eye diseases
Biometals ( IF 4.1 ) Pub Date : 2021-07-23 , DOI: 10.1007/s10534-021-00331-y
S U Nabi 1 , A Jan 1 , S Muzamil 2 , R Razaq 2 , A Muhee 1 , T Ashraf 3 , S Ahmad 4 , D M Makhdoomi 5 , N Nazir Shah 6 , Q Syed 7
Affiliation  

The present study was designed to evaluate the age-related changes in biometal and antimicrobial peptide (cathelicidin) concentration and their role in oxidative cum pro-inflammatory cascade in an ovine animal model. Clinically healthy ovine (n = 126) were grouped as Group I (n = 55, age = up to 3 years), Group II (n = 52, age = above 3-below 6 years) and Group III (n = 19, age = 6 years above). Samples (aqueous humour and lens of the eye) were collected stored at − 80 °C till further analysis. In aqueous humour, the concentration of zinc (p < 0.001 in group III), copper (p < 0.05 in group II and p < 0.001 group III) and iron (p < 0.05 in group III) were significantly increased compared to group I. While as the concentration of magnesium were significantly decreased in group II (p < 0.001) and group III (p < 0.05) compared to group I. Similarly in eye lens the level of copper remained uniform as no significant change was observed across different age groups, while as significantly elevated levels of iron were observed in group III (p < 0.001) compared to group I. whereas, levels of lens Zinc (p < 0.05 in group II) and magnesium (p < 0.05 in group III and p < 0.001 in group II) were significantly decreased compared to group I. Age-dependent increase in levels of oxidation products which include advanced oxidation protein products (AOPP) in aqueous humour and lenses of group II and group III (p < 0.001) and MDA in aqueous humour of group III (p < 0.05) were found compared to levels recorded in group I. In contrast, levels of antioxidants which include lens vitamin C in group II and group III (p < 0.01) and lens superoxide dismutase (SOD) in group III (p < 0.001) were significantly increased compared to group I. Levels of pro-inflammatory cytokines in aqueous humour revealed significantly (p < 0.001) age-dependent increase in IL-1, IL-6 and TNF-α elevated in group III, and group II as compared to group I, However, cathelicidin level in aqueous humour of group III and group II were significantly (p < 0.001) lower as compared to groups I. Furthermore,the present study observed significant (p < 0.05) metal–metal positive interaction between copper levels in lens with levels of (iron and magnesium) in aqueous humour, levels of Zn in lens with levels of Zn in aqueous humour, levels of Mg in lens with levels of (Cu, Zn and Mg) in aqueous humour. In addition,the present study reports significantly negative interaction between levels of lens Fe with levels of lens magnesium level, aqueous humour magnesium level and levels of copper in aqueous humour. A significantly positive correlation was observed between oxidative markers and pro-inflammatory cytokine levels, while a significant negative correlation was observed between antioxidant defence markers and pro-inflammatory cytokine. These results suggest the essential role of age-related changes in biometal levels, oxidative stress and pro-inflammatory cytokines. These changes might help understand age-related changes in pathogenesis and effective targeting of pathogenetic pathways in ocular diseases.



中文翻译:

生物金属在羊老化眼免疫和炎症反应激活中的作用:了解人类老年眼病的潜在模型

本研究旨在评估与年龄相关的生物金属和抗菌肽(cathelicidin)浓度变化及其在绵羊动物模型中氧化和促炎级联反应中的作用。临床上健康的绵羊(n = 126)分为第一组(n = 55,年龄 = 最多 3 岁)、第二组(n = 52,年龄 = 3 岁以上 - 6 岁以下)和第三组(n = 19,年龄 = 6 岁以上)。收集样品(房水和眼睛晶状体)储存在 - 80 °C 直至进一步分析。在房水中,与第一组相比,锌(第三组 p < 0.001)、铜(第二组 p < 0.05 和第三组 p < 0.001)和铁(第三组 p < 0.05)的浓度显着增加。而第二组(p < 0.001)和第三组(p < 0.001)的镁浓度显着降低。01) 和晶状体超氧化物歧化酶 (SOD) 组 III (p < 0.001) 与组 I 相比显着增加。房水中促炎细胞因子水平显着 (p < 0.001) IL-1 的年龄依赖性增加, III 组和 II 组的 IL-6 和 TNF-α 与 I 组相比升高,但 III 组和 II 组房水中的导管素水平与 I 组相比显着降低(p < 0.001)。此外,本研究观察到晶状体中的铜含量与房水中的(铁和镁)含量、晶状体中的锌含量与房水中的锌含量、晶状体中的镁含量之间存在显着的(p < 0.05)金属-金属正相互作用与房水中的 (Cu、Zn 和 Mg) 水平有关。此外,本研究报告了晶状体铁水平与晶状体镁水平、房水镁水平和房水中铜水平之间的显着负相互作用。氧化标志物与促炎细胞因子水平呈显着正相关,而抗氧化防御标志物与促炎细胞因子呈显着负相关。这些结果表明与年龄相关的生物金属水平、氧化应激和促炎细胞因子变化的重要作用。这些变化可能有助于了解与年龄相关的发病机制变化和眼部疾病发病途径的有效靶向。氧化标志物与促炎细胞因子水平呈显着正相关,而抗氧化防御标志物与促炎细胞因子呈显着负相关。这些结果表明与年龄相关的生物金属水平、氧化应激和促炎细胞因子变化的重要作用。这些变化可能有助于了解与年龄相关的发病机制变化和眼部疾病发病途径的有效靶向。氧化标志物与促炎细胞因子水平呈显着正相关,而抗氧化防御标志物与促炎细胞因子呈显着负相关。这些结果表明与年龄相关的生物金属水平、氧化应激和促炎细胞因子变化的重要作用。这些变化可能有助于了解与年龄相关的发病机制变化和眼部疾病发病途径的有效靶向。

更新日期:2021-07-23
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