[1]邱宇,高洪莲,于睿,等.抗血管内皮生长因子玻璃体内注射对形觉剥夺性近视豚鼠视网膜中多巴胺水平的影响[J].眼科新进展,2022,42(2):113-117.[doi:10.13389/j.cnki.rao.2022.0023]
　QIU Yu,GAO Honglian,YU Rui,et al.Effect of intravitreal injection of anti-vascular endothelial growth factor on the dopamine level in the retina of guinea pigs with form deprivation myopia[J].Recent Advances in Ophthalmology,2022,42(2):113-117.[doi:10.13389/j.cnki.rao.2022.0023]
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抗血管内皮生长因子玻璃体内注射对形觉剥夺性近视豚鼠视网膜中多巴胺水平的影响/HTML
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《眼科新进展》[ISSN:1003-5141/CN:41-1105/R]

卷:
42卷
期数:
2022年2期
页码:
113-117
栏目:
实验研究
出版日期:
2022-02-05

文章信息/Info

Title:
Effect of intravitreal injection of anti-vascular endothelial growth factor on the dopamine level in the retina of guinea pigs with form deprivation myopia
作者:
邱宇; 高洪莲; 于睿; 李欣蒙; 崔钰莹; 张磊
256600　山东省滨州市，滨州医学院附属医院（第一临床医学院）眼科（邱宇，于睿，李欣蒙，崔钰莹，张磊）；256600　山东省滨州市，滨州医学院附属医院（第一临床医学院）医学研究中心（高洪莲）
Author(s):
QIU Yu1; GAO Honglian2; YU Rui1; LI Xinmeng1; CUI Yuying1; ZHANG Lei1
1.Department of Ophthalmology，the Affiliated Hospital of Binzhou Medical University,Binzhou 256600,Shandong Province,China
2.Medical Research Center,the Affiliated Hospital of Binzhou Medical University,Binzhou 256600,Shandong Province,China
关键词:
形觉剥夺性近视; 血管内皮生长因子; 多巴胺; 康柏西普; 豚鼠
Keywords:
form deprivation myopia;  vascular endothelial growth factor;  dopamine;  Conbercept;  guinea pigs
分类号:
R778.1
DOI:
10.13389/j.cnki.rao.2022.0023
文献标志码:
A
摘要:
目的　探讨抗血管内皮生长因子融合蛋白康柏西普（Conbercept）玻璃体内注射对形觉剥夺性近视（FDM)豚鼠视网膜中多巴胺（DA）水平的影响。方法　选取3周龄三色豚鼠60只，按照随机数字表法分为空白对照组、FDM组、FDM+生理盐水组、FDM+Conbercept组，每组15只。空白对照组豚鼠双眼不作任何处理，其余3组豚鼠用半透明乳胶气球遮盖右眼2周建立FDM模型，左眼不做处理。FDM+生理盐水组豚鼠遮盖前右眼玻璃体内注射生理盐水0.002 mL，FDM+Conbercept组豚鼠遮盖前右眼玻璃体内注射Conbercept 0.02 mg（0.002 mL）。分别于遮盖前和造模结束后测量豚鼠右眼眼球屈光度和眼轴长度，测量后处死豚鼠并摘取眼球，采用免疫荧光法检测各组豚鼠视网膜中DA限速酶酪氨酸羟化酶（TH）的相对表达量，采用高效液相色谱法分析DA、3，4-二羟基苯乙酸（DOPAC）的含量及DA代谢率。结果　遮盖前，4组豚鼠的右眼屈光度数和眼轴长度差异均无统计学意义（均为P>0.05）。遮盖2周后，与空白对照组相比，FDM组豚鼠右眼近视度升高，眼轴长度延长，TH、DA、DOPAC相对表达量均减少，差异均有统计学意义（均为P<0.05）；与FDM组相比，FDM+生理盐水组豚鼠屈光度、眼轴长度、TH、DA和DOPAC的相对表达水平差异均无统计学意义（均为P>0.05）；与FDM组和FDM+生理盐水组相比，FDM+Conbercept组豚鼠右眼近视度更高，眼轴长度更长，TH、DA、DOPAC相对表达量均减少，差异均有统计学意义（均为P<0.05）；4组豚鼠DA代谢率差异均无统计学意义（均为P>0.05）。结论　Conbercept玻璃体内注射可降低FDM豚鼠视网膜中的DA水平，并导致豚鼠眼轴延长、近视度升高。
Abstract:
Objective　To investigate the effect of intravitreal injection of anti-vascular endothelial growth factor fusion protein, Conbercept, on the dopamine (DA) level in the retina of guinea pigs with form deprivation myopia (FDM).Methods　A total of 60 three-week-old tricolor guinea pigs were randomly divided into the blank control group, FDM group, FDM+normal saline group, and FDM+Conbercept group using the random number table method, with 15 in each group. Guinea pigs in the blank control group did not receive any treatment on both eyes, while the right eyes of guinea pigs in the remaining three groups were covered by translucent latex balloons for 2 weeks to establish FDM models, with left eyes untreated. In the FDM+normal saline group, 0.002 mL of normal saline was injected into the vitreous cavity of the right eyes before cove-ring, while in the FDM+Conbercept group, 0.02 mg (0.002 mL) of Conbercept was injected into the vitreous cavity of the right eyes before covering. The refractive power and axial length of right eyes in all groups were measured respectively before covering and after the establishment of models. After these measurements, the guinea pigs were sacrificed, and their eyeballs were extracted. The relative expression level of tyrosine hydroxylase (TH) in the retina of all guinea pigs was detected by immunofluorescence assay. The content levels of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) as well as the DA metabolism were analyzed by high performance liquid chromatography.Results　Before covering, no significant difference was observed in the refractive power and axial length of right eyes in all groups (all P>0.05). After covering for two weeks, compared with the blank control group, the degree of myopia and axial length of right eyes in the FDM group were significantly increased, and the relative expression levels of TH, DA, and DOPAC were significantly decreased (all P<0.05). Compared with the FDM group, no significant difference was observed in the refractive power, axial length, and the relative expression levels of TH, DA, and DOPAC in the FDM+normal saline group (all P>0.05). Compared with the FDM group and the FDM+normal saline group, right eyes in the FDM+Conbercept group had a greater degree of myopia and a longer axis, while the relative expression levels of TH, DA, and DOPAC were significantly reduced (all P<0.05). No significant difference in the DA metabolism was observed among all groups (all P>0.05).Conclusion　Intravitreal injection of Conbercept can reduce the DA level in the retina of FDM guinea pigs, resulting in axial elongation and increased myopia.

参考文献/References:

［1］　MODJTAHEDI B S,FERRIS F L 3RD,HUNTER D G,FONG D S.Public health burden and potential interventions for myopia［J］.Ophthalmology,2018,125(5):628-630.
［2］　RESNIKOFF S,JONAS J B,FRIEDMAN D,HE M,JONG M,NICHOLS J J,et al.Myopia-a 21st century public health issue［J］.Invest Ophthalmol Vis Sci,2019,60(3):Mi-Mii.
［3］　MORGAN I G,FRENCH A N,ASHBY R S,GUO X,DING X,HE M,et al.The epidemics of myopia:Aetiology and prevention［J］.Prog Retin Eye Res,2018,62:134-149.
［4］　HOLDEN B A,FRICKE T R,WILSON D A,JONG M,NAIDOO K S,SANKARIDURG P,et al.Global prevalence of myopia and high myopia and temporal trends from 2000 through 2050［J］.Ophthalmology,2016,123(5):1036-1042.
［5］　BAIRD P N,SAW S M,LANCA C,GUGGENHEIM J A,SMITH III E L,ZHOU X,et al.Myopia［J］.Nat Rev Dis Primers,2020,6(1):99.
［6］　ZHOU X,PARDUE M T,IUVONE P M,QU J.Dopamine signaling and myopia development:what are the key challenges［J］.Prog Retin Eye Res,2017,61:60-71.
［7］　GAO Q,LIU Q,MA P,ZHONG X,WU J,GE J.Effects of direct intravitreal dopamine injections on the development of lid-suture induced myopia in rabbits［J］.Graefes Arch Clin Exp Ophthalmol,2006,244(10):1329-1335.
［8］　THOMSON K,KAROUTA C,ASHBY R.Form-deprivation and lens-induced myopia are similarly affected by pharmacological manipulation of the dopaminergic system in chicks［J］.Invest Ophthalmol Vis Sci,2020,61(12):4.
［9］　PILTONEN M,PLANKEN A,LESKEL O,MYHNEN T T,HNNINEN A L,AUVINEN P,et al.Vascular endothelial growth factor c acts as a neurotrophic factor for dopamine neurons in vitro and in vivo［J］.Neuroscience,2011,192:550-563.
［10］　MATEO I,LLORCA J,INFANTE J,RODRGUEZ-RODRGUEZ E,FERNNDEZ-VIADERO C,PEA N,et al.Low serum VEGF levels are associated with alzheimer’s disease［J］.Acta Neurol Scand,2007,116(1):56-58.
［11］　MCBRIEN N A,COTTRIALL C L,ANNIES R.Retinal acetylcholine content in normal and myopic eyes:a role in ocular growth control?［J］.Vis Neurosci,2001,18(4):571-580.
［12］　DONG F,ZHI Z,PAN M,XIE R,QIN X,LU R,et al.Inhibition of experimental myopia by a dopamine agonist:Different effectiveness between form deprivation and hyperopic defocus in guinea pigs［J］.Mol Vis,2011,17:2824-2834.
［13］　MCCARTHY C S,MEGAW P,DEVADAS M,MORGAN I G.Dopaminergic agents affect the ability of brief periods of normal vision to prevent form-deprivation myopia［J］.Exp Eye Res,2007,84(1):100-107.
［14］　THOMSON K,MORGAN I,KAROUTA C,ASHBY R.Levodopa inhibits the development of lens-induced myopia in chicks［J］.Sci Rep,2020,10(1):13242.
［15］　HUPP-GOURGUES F,COUD G,LACHAPELLE P,CASANOVA C.Effects of the intravitreal administration of dopaminergic ligands on the b-wave amplitude of the rabbit electroretinogram［J］.Vision Res,2005,45(2):137-145.
［16］　ZHANG S,YANG J,REINACH P S,WANG F,ZHANG L,FAN M,et al.Dopamine receptor subtypes mediate opposing effects on form deprivation myopia in pigmented guinea pigs［J］.Invest Ophthalmol Vis Sci,2018,59(11):4441-4448.
［17］　BERGEN M A,PARK H N,CHAKRABORTY R,LANDIS E G,SIDHU C,HE L,et al.Altered refractive development in mice with reduced levels of retinal dopamine［J］.Invest Ophthalmol Vis Sci,2016,57(10):4412-4419.
［18］　OSINGA T E,LINKS T P,DULLAART R P F,PACAK K,VAN DER HORST-SCHRIVERS A N A,KERSTENS M N,et al.Emerging role of dopamine in neovascularization of pheochromocytoma and paraganglioma［J］.FASEB J,2017,31(6):2226-2240.
［19］　MEGAW P,MORGAN I,BOELEN M.Vitreal dihydroxyphenylacetic acid (dopac) as an index of retinal dopamine release［J］.J Neurochem,2001,76(6):1636-1644.
［20］　FELDKAEMPER M,SCHAEFFEL F.An updated view on the role of dopamine in myopia［J］.Exp Eye Res,2013,114:106-119.
［21］　MELINCOVICI C S,BO CA A B, U MAN S,MRGINEAN M,MIHU C,ISTRATE M,et al.Vascular endothelial growth factor (VEGF)-key factor in normal and pathological angiogenesis［J］.Rom J Morphol Embryol,2018,59(2):455-467.
［22］　TARALLO V,DE FALCO S.The vascular endothelial growth factors and receptors family:up to now the only target for anti-angiogenesis therapy［J］.Int J Biochem Cell Biol,2015,64:185-189.
［23］　ECHEVERRIA V,BARRETO G E,AVILA-RODRIGUEZC M,TARASOV V V,ALIEV G.Is VEGF a key target of cotinine and other potential therapies against alzheimer disease?［J］.Curr Alzheimer Res,2017,14(11):1155-1163.
［24］　NISHIJIMA K,NG Y S,ZHONG L,BRADLEY J,SCHUBERT W,JO N,et al.Vascular endothelial growth factor-a is a survival factor for retinal neurons and a critical neuroprotectant during the adaptive response to ischemic injury［J］.Am J Pathol,2007,171(1):53-67.
［25］　YASUHARA T,SHINGO T,KOBAYASHI K,TAKEUCHI A,YANO A,MURAOKA K,et al.Neuroprotective effects of vascular endothelial growth factor (VEGF) upon dopaminergic neurons in a rat model of parkinson’s disease［J］.Eur J Neurosci,2004,19(6):1494-1504.
［26］　ZACHARY I.Neuroprotective role of vascular endothelial growth factor:signalling mechanisms,biological function,and therapeutic potential［J］.Neurosignals,2005,14(5):207-221.
［27］　CAI S,YANG Q,LI X,ZHANG Y.The efficacy and safety of aflibercpt and conbercept in diabetic macular edema［J］.Drug Des Devel Ther,2018,12:3471-3483.

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备注/Memo

备注/Memo:
山东省医药卫生科技发展计划项目（编号：2016WS0022）
更新日期/Last Update: 2022-02-05