血管内皮生长因子-B对形觉剥夺性近视豚鼠视网膜中多巴胺水平的影响

doi:10.6040/j.issn.1671-7554.0.2024.0245

摘要/Abstract

摘要： 目的研究玻璃体腔注射血管内皮生长因子-B(vascular endothelial growth factor-B, VEGF-B)对形觉剥夺性近视(form-deprivation myopia, FDM)豚鼠视网膜中多巴胺(dopamine, DA)水平的影响。方法随机选取健康的3周龄豚鼠147只,雌雄不限,随机分为7个组,每组21只。空白组双眼不予干预,其余6组使用半透明乳胶气球套头遮盖豚鼠右眼14 d建立FDM模型。造模前对PBS组、0.25 ng组、2.5 ng组、25 ng组、50 ng组右眼玻璃体腔注射PBS缓冲液2.5 μL、VEGF-B 0.25 ng、2.5 ng、25 ng、50 ng。遮盖前后分别测量造模眼屈光度与眼轴长度,14 d后采用免疫荧光法检测酪氨酸羟化酶(tyrosine hydroxylase, TH)阳性细胞数量、免疫印记法检测视网膜TH的蛋白表达情况、HE染色观察视网膜血管内皮细胞核数、高效液相色谱法测定DA与3,4-二羟基苯乙酸(3,4-dihydroxyphenylacetic acid, DOPAC)的含量及 DA 代谢率。结果造模前,7组豚鼠右眼屈光度与眼轴长度均无显著差异(P>0.05)。造模完成后与空白组相比,FDM组、PBS组屈光不正向近视侧偏移,眼轴增长,TH、DA、DOPAC含量均降低(P<0.05);与FDM组相比,0.25 ng组、2.5 ng组、25 ng组、50 ng组豚鼠遮盖眼近视程度均降低,眼轴增长趋势被抑制,TH、DA、DOPAC表达量均增加(P均<0.05),随着VEGF-B浓度的升高,眼轴增长所受抑制程度逐渐增加,近视程度逐渐减轻,TH等检测指标的表达水平均逐渐升高。7组豚鼠视网膜DA代谢率、视网膜内血管内皮细胞核数差异均无统计学意义(P>0.05)。结论玻璃体腔注射VEGF-B可使FDM豚鼠视网膜中的DA含量升高、眼轴增长程度减轻,从而抑制FDM豚鼠的近视发展,且不会诱导新生血管生成,其中50 ng组VEGF-B对DA的促进作用更明显。

关键词: 血管内皮生长因子-B, 形觉剥夺性近视, 多巴胺, 视网膜, 酪氨酸羟化酶

Abstract: Objective To study the effect of intravitreal injection of vascular endothelial growth factor-B(VEGF-B)on the level of dopamine(DA)in the retina of form-deprivation myopia(FDM)guinea pigs. Methods A Total of 147 healthy 3-week-old guinea pigs, male or female, were selected and randomly divided into 7 groups, with 21 guinea pigs in each group. The eyes of guinea pins in the blank group were not intervened,and the right eyes of the guinea pins in other 6 groups were covered with translucent latex balloon for 14 days to establish the FDM model. After preparation, 2.5 μL of PBS buffer and VEGF-B at concentrations of 0.25 ng, 2.5 ng, 5 ng and 50 ng were intravitreally injected into the right eye of the guinee pigs in the PBS group as well as the groups of 0.25 ng, 2.5 ng, 25 ng and 50 ng. Ocular refraction and axial length were recorded in both eyes of each animal before and after modeling. After 14 days, immunofluorescence was used to detect the number of tyrosine hydroxylase positive cells; Western blotting was used to detect the expression of TH protein in the retina; HE staining was used to observe the number of retinal vascular endothelial cell nuclei; and high performance liquid chromatography was used to determine DA and 3,4-dihydroxyphenylacetic acid(DOPAC)content and DA metabolic rate. Results Before modeling,there was no significant difference in the diopter and axial length of the right eye among the 7 groups(P>0.05). After modeling, compared with the blank group, refractive error was shifted to the myopic side in the FDM and PBS groups, the axes of the eyes grew, and the TH, DA, and DOPAC levels were reduced(P<0.05). Compared to the FDM group, the guinea pigs in the VEGF-B groups(0.25 ng, 2.5 ng, 25 ng and 50 ng)exhibited a decrease in myopia progression and inhibition of axial elongation, accompanied by increased expression levels of TH, DA, and DOPAC(all P<0.05). As the concentration of VEGF-B increased, there was a gradual enhancement in the suppression of axial growth and reduction in myopia severity while observing a progressive elevation in TH expression and other indicators. There was no significant difference in the metabolic rate of DA and the number of retinal vascular endothelial cell nuclei among the 7 groups(P>0.05). Conclusion The intravitreal injection of VEGF-B can enhance retinal DA levels and inhibit axial elongation, thereby effectively suppressing myopia development in FDM guinea pigs without inducing neovascularization. Notably, the impact of VEGF-B on DA was particularly pronounced in the 50 ng group.

Key words: Vascular endothelial growth factor-B, Form deprivation myopia, Dopamine, Retina, Tyrosine hydroxylase

中图分类号:

R774.1

姜俊,高洪莲,孙瑞婷,孙昕,彭庆生,张守宽,张磊. 血管内皮生长因子-B对形觉剥夺性近视豚鼠视网膜中多巴胺水平的影响[J]. 山东大学学报 (医学版), 2024, 62(7): 62-71.

JIANG Jun, GAO Honglian, SUN Ruiting, SUN Xin, PENG Qingsheng, ZHANG Shoukuan, ZHANG Lei. Effect of vascular endothelial growth factor-B on the dopamine level in the retina of guinea pigs with form-deprivation myopia[J]. Journal of Shandong University (Health Sciences), 2024, 62(7): 62-71.

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