Targeting long non-coding RNA MALAT1 alleviates retina neurodegeneration in diabetic mice
Targeting long non-coding RNA MALAT1 alleviates retina neurodegeneration in diabetic mice
复制标题
靶向长非编码RNA MALAT1可减轻糖尿病小鼠的视网膜神经变性
DOI：
10.18240/ijo.2020.02.03
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发表时间：
2020-02-18
影响因子：
1.4
通讯作者：
Shi, Ke
中科院分区：
文献类型：
--
作者：
Zhang, Yu-Lan;Hu, Han-Ying;Shi, Ke
目的：方法：将36只8周龄C57 BL/6小鼠随机分为正常对照组、糖尿病对照组、糖尿病乱序小干扰RNA（scrambled small interfering RNAs，siRNA）组和糖尿病MALAT 1-siRNA组。糖尿病MALAT 1-siRNA组在腹腔注射链脲佐菌素诱导糖尿病后，玻璃体内注射1 μ L 20 μ mol/L MALAT 1 siRNA，糖尿病乱序siRNA组注射等量乱序siRNA。糖尿病诱导后16周进行视网膜电图检查感光细胞功能。采用真实的时间聚合酶链反应检测MALAT 1的表达。用免疫荧光法检测球果形态学变化。结果：糖尿病对照组小鼠视网膜MALAT 1表达上调，而MALAT 1-siRNA组小鼠视网膜MALAT 1表达较糖尿病对照组下降91.48%。糖尿病MALAT 1-siRNA和糖尿病对照小鼠在暗视和明视视网膜电图中显示出比正常对照小鼠低的a波和b波振幅，而糖尿病MALAT 1-siRNA小鼠显示出比糖尿病对照小鼠高的振幅。形态学检查显示，糖尿病MALAT 1-siRNA组和糖尿病对照组小鼠ONL厚度低于正常对照组小鼠。然而，糖尿病MALAT 1-siRNA小鼠的ONL厚度大于糖尿病对照小鼠。结论：抑制MALAT 1基因的表达可减轻糖尿病视网膜光感受器的损伤，从而减轻糖尿病视网膜神经退行性变。
AIM: To observe the effect of inhibiting long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1(MALAT1) on diabetic neurodegeneration.METHODS: Thirty-six 8-week-old C57BL/6 mice were randomly divided into normal control, diabetic control, diabetic scrambled small interfering RNAs (siRNAs) and diabetic MALAT1-siRNA groups. After diabetic induction with streptozocin intraperitoneally-injection, the diabetic MALAT1-siRNA group was intravitreally injected with 1 mu L 20 mu mol/L MALAT1 siRNA, and the diabetic scrambled siRNA group was injected with the same amount of scrambled siRNA. Electroretinography was performed to examine photoreceptor functions 16wk after diabetes induction. MALAT1 expression was detected via real time polymerase chain reaction. Cone morphological changes were examined using immunofluorescence. Rod morphological changes were examined by determining outer nuclear layer (ONL) thickness.RESULTS: The upregulation of retinal MALAT1 expression was detected in the diabetic control mice, while MALAT1 expression in the diabetic MALAT1-siRNA mice was decreased by 91.48% compared to diabetic control mice. The diabetic MALAT1-siRNA and diabetic control mice showed lower a-wave and b-wave amplitudes than did the normal control mice in scotopic and photopic electroretinogram, while the diabetic MALAT1-siRNA mice showed higher amplitudes than diabetic control mice. Morphological examination revealed that ONL thickness in the diabetic MALAT1-siRNA and diabetic control mice was lower than normal control mice. However, ONL thickness was greater in the diabetic MALAT1-siRNA mice than diabetic control mice. Moreover, the diabetic control mice performed a sparser cone cell arrangement and shorter outer segment morphology than diabetic MALAT1-siRNA mice.CONCLUSION: Inhibiting retinal MALAT1 results in mitigative effects on the retinal photoreceptors, thus alleviating diabetic neurodegeneration.