形觉剥夺性高度近视豚鼠巩膜形态改变及缺氧诱导因子-1α和氧自由基在高度近视中的作用
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摘要
目的观察形觉剥夺性高度近视(form deprivation high myopia,FDHM)豚鼠巩膜形态变化,探讨缺氧诱导因子-1α(hypoxia-inducible factor-1α,HIF-1α)及氧自由基在高度近视中的作用。方法将豚鼠适应性饲养1周后,随机分为空白对照组(25只)和模型组(25只)。模型组豚鼠右眼行眼睑缝合,所有模型组豚鼠均选择右眼作为FDHM组,对侧眼为自身对照组。空白对照组豚鼠不做任何处理。于造模前及造模后8周采用检影镜测量屈光度,A超进行生物测量。形觉剥夺8周以后处死豚鼠,观察巩膜形态和超微结构的变化,测定巩膜HIF-1α相对表达量,超氧化物歧化酶(superoxide dismutase,SOD)活力及丙二醛(malondialdehyde,MDA)的含量。结果豚鼠形觉剥夺8周以后,FDHM组屈光度从(+3.59±0.33)D变为(-7.96±0.55)D,明显高于空白对照组(+0.89±0.32)D、自身对照组(-0.55±0.49)D(均为P<0.05);玻璃体腔深度为(4.12±0.13)mm明显高于空白对照组(3.71±0.23)mm和自身对照组(3.93±0.04)mm(均为P<0.05);眼轴长度为(8.93±0.22)mm明显长于空白对照组(7.95±0.37)mm和自身对照组(8.01±0.15)mm(均为P<0.05)。巩膜组织明显变薄,细胞外基质增多,成纤维细胞密度降低,胶原纤维平均直径减小。FDHM组巩膜中HIF-1α相对表达量、MDA含量明显高于空白对照组和自身对照组,SOD活力明显低于空白对照组和自身对照组(均为P<0.05)。结论形觉剥夺8周后,豚鼠FDHM眼近视度数明显增加,玻璃体腔深度增加,眼轴延长,巩膜形态发生病理性变化;HIF-1α、SOD、MDA可能参与了FDHM的形成。
Objective To observe the morphological structure changes in sclera of form deprivation high myopia(FDHM) guinea pigs and investigate the role of hypoxia inducible factor-1α(HIF-1α) and oxygen free radical in the formation of high myopia.Methods After 1 week of adaptive feeding,guinea pigs were randomly divided into blank control group(25 cases) and model group(25 cases).In model group,the right eyes of guinea pigs were sutured and selected as the FDHM group,and the left eyes were served as self-control group.Guinea pigs in the blank control group were without any treatment.At the beginning and 8 weeks after modeling,the diopter and every index of eyeball were measured by retinoscopy and ultrasonometry A respectively.The guinea pigs were sacrificed after form deprivation for 8 weeks.Changes of scleral morphology and ultrastructural features were observed after guinea pigs were sacrificed 8 weeks after form deprivation.The relative expression of HIF-1α,the activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA) in sclera were detected.Results After stitched for 8 weeks,the diopter of FDHM group was changed from(+3.59±0.33)D to(-7.96±0.55)D,and significantly higher than that in blank control group(+0.89±0.32)D and self-control group(-0.55±0.49)D(all P<0.05);The vitreous chamber depth of FDHM group was(4.12±0.13)mm,and significantly longer than that in blank control group(3.71±0.23)mm and self-control group(3.93±0.04)mm(all P<0.05).The axial length of FDHM group was(8.93±0.22)mm,and significantly longer than that in blank control group(7.95±0.37)mm and self-control group(8.01±0.15)mm(all P<0.05).Scleral tissues became markedly thinner,extracellular matrix increased,fibroblast density and average diameter of collagen fibers decreased.In FDHM group,the relative expression of HIF-1α and content of MDA in sclera were significantly higher than those in blank control group and self-control group,the activity of SOD was significantly lower than that in blank control group and self-control group(all P<0.05).Conclusion After form deprivation for 8 weeks,the diopter,the vitreous chamber depth and axial length of FDHM group are significantly increased,and pathological changes in scleral morphology are observed,which indicates HIF-1α,SOD and MDA may participate in the formation of FDHM.
Objective To observe the morphological structure changes in sclera of form deprivation high myopia(FDHM) guinea pigs and investigate the role of hypoxia inducible factor-1α(HIF-1α) and oxygen free radical in the formation of high myopia.Methods After 1 week of adaptive feeding,guinea pigs were randomly divided into blank control group(25 cases) and model group(25 cases).In model group,the right eyes of guinea pigs were sutured and selected as the FDHM group,and the left eyes were served as self-control group.Guinea pigs in the blank control group were without any treatment.At the beginning and 8 weeks after modeling,the diopter and every index of eyeball were measured by retinoscopy and ultrasonometry A respectively.The guinea pigs were sacrificed after form deprivation for 8 weeks.Changes of scleral morphology and ultrastructural features were observed after guinea pigs were sacrificed 8 weeks after form deprivation.The relative expression of HIF-1α,the activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA) in sclera were detected.Results After stitched for 8 weeks,the diopter of FDHM group was changed from(+3.59±0.33)D to(-7.96±0.55)D,and significantly higher than that in blank control group(+0.89±0.32)D and self-control group(-0.55±0.49)D(all P<0.05);The vitreous chamber depth of FDHM group was(4.12±0.13)mm,and significantly longer than that in blank control group(3.71±0.23)mm and self-control group(3.93±0.04)mm(all P<0.05).The axial length of FDHM group was(8.93±0.22)mm,and significantly longer than that in blank control group(7.95±0.37)mm and self-control group(8.01±0.15)mm(all P<0.05).Scleral tissues became markedly thinner,extracellular matrix increased,fibroblast density and average diameter of collagen fibers decreased.In FDHM group,the relative expression of HIF-1α and content of MDA in sclera were significantly higher than those in blank control group and self-control group,the activity of SOD was significantly lower than that in blank control group and self-control group(all P<0.05).Conclusion After form deprivation for 8 weeks,the diopter,the vitreous chamber depth and axial length of FDHM group are significantly increased,and pathological changes in scleral morphology are observed,which indicates HIF-1α,SOD and MDA may participate in the formation of FDHM.
引文
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[12] WU H,CHEN W,ZHAO F,ZHOU Q,REINACH P S,DENG L,et al.Scleral hypoxia is a target for myopia control[J].Proc Natl Acad Sci USA,2018,115(30):E7091-E7100.
[13] TSUBOTA K.Anti-aging approach for ocular disorders:from dry eye to retinitis pigmentosa and myopia[J].Nippon Ganka Gakkai Zasshi,2017,121(3):232-248.
[14] SRINIVASALU N,MCFADDEN S A,MEDCALF C,FUCHS L,CHUNG J,PHILIP G,et al.Gene expression and pathways underlying form deprivation myopia in the guinea pig sclera[J].Invest Ophthalmol Vis Sci,2018,59(3):1425-1434.
[15] XIAO H,FAN Z Y,TIAN X D,XU Y C.Comparison of form-deprived myopia and lens-induced myopia in guinea pigs[J].Int J Ophthalmol,2014,2(7):245-250.
[16] REN Y,XIE R,ZHOU X,PAN M,LU F.Spontaneous high myopia in one eye will affect the development of form deprivation myopia in the fellow eye[J].Curr Eye Res,2011,36(6):513-521.
[17] KRESYUN N V,GODLEVSKII L S.Superoxide dismutase and catalase activities in the retina during experimental diabetes and electric stimulation of the paleocerebellar cortex[J].Bull Exp Biol Med,2014,158(2):206-208.
[18] HO P D,PIL S J,TAEK K I.Association of plasma malondialdehyde with ARMS2 genetic variants and phenotypes in polypoidal choroidal vasculopathy and age-related macular degeneration[J].Retina,2014,34(6):1167-1176.
[19] ZHAO H L,WANG R Q,WU M Q,JIANG J.Dynamic changes of ocular biometric parameters:a modified form-deprivation myopia model of young guinea pigs[J].Int J Ophthalmol,2011,4(5):484-488.
[2] SHERMAN S M,NORTON T T,CASAGRANDE V A.Myopia in the lid-sutured tree shrew (Tupaia glis)[J].Brain Res,1977,124(1):154-157.
[3] MARSH-TOOTLE W L,NORTON T T.Refractive and structural measures of lid-suture myopia in tree shrew[J].Invest Ophthalmol Vis Sci,1989,30(10):2245-2257.
[4] MORGAN I,KUCHARSKI R,KRONGKAEW N,FIRTH S I,MEGAW P,MALESZKA R.Screening for differential gene expression during the development of form-deprivation myopia in the chicken[J].Optom Vis Sci,2004,81(2):148-155.
[5] YU Y,LI M,GUAN H J,CHEN H.Expression and role of Egr-1 gene in retina of flicker light-induced eyes in mice[J].Chin J Exp Ophthalmol,2015,33(7):621-626.俞莹,李曼,管怀进,陈辉.小鼠闪烁光诱导眼视网膜中Egr-1基因的表达及作用[J].中华实验眼科杂志,2015,33(7):621-626.
[6] WANG X,XU G,FAN J,ZHANG M.Mechanical stretching induces matrix metalloproteinase-2 expression in rat retinal glial (Muller) cells[J].Neuroreport,2013,24(5):224-228.
[7] WANG K K,METLAPALLY R,WILDSOET C F.Expression profile of the integrin receptor subunits in the guinea pig sclera[J].Curr Eye Res,2017,42(6):857-863.
[8] FRANCISCO B M,SALVADOR M,AMPARO N.Oxidative stress in myopia[J].Oxid Med Cell Longev,2015,2015:750637.
[9] SCHAEFFEL F,FELDKAEMPER M.Animal models in myopia research[J].Clin Exp Optom,2015,98(6):507-517.
[10] GOLDSCHMIDT E,JACOBSEN N.Genetic and environmental effects on myopia development and progression[J].Eye (Lond),2014,28(2):126-133.
[11] CHINESE OPTOMETRIC ASSOCIATION,CHINESE OPHTHA-LMOLOGICAL SOCIETY.Consensus:prevention and control of high myopia[J].Chin J Optom Ophthalmol Vis Sci,2017,19(7):385-389.中华医学会眼科学分会眼视光学组.重视高度近视防控的专家共识(2017)[J].中华眼视光学与视觉科学杂志,2017,19(7):385-389.
[12] WU H,CHEN W,ZHAO F,ZHOU Q,REINACH P S,DENG L,et al.Scleral hypoxia is a target for myopia control[J].Proc Natl Acad Sci USA,2018,115(30):E7091-E7100.
[13] TSUBOTA K.Anti-aging approach for ocular disorders:from dry eye to retinitis pigmentosa and myopia[J].Nippon Ganka Gakkai Zasshi,2017,121(3):232-248.
[14] SRINIVASALU N,MCFADDEN S A,MEDCALF C,FUCHS L,CHUNG J,PHILIP G,et al.Gene expression and pathways underlying form deprivation myopia in the guinea pig sclera[J].Invest Ophthalmol Vis Sci,2018,59(3):1425-1434.
[15] XIAO H,FAN Z Y,TIAN X D,XU Y C.Comparison of form-deprived myopia and lens-induced myopia in guinea pigs[J].Int J Ophthalmol,2014,2(7):245-250.
[16] REN Y,XIE R,ZHOU X,PAN M,LU F.Spontaneous high myopia in one eye will affect the development of form deprivation myopia in the fellow eye[J].Curr Eye Res,2011,36(6):513-521.
[17] KRESYUN N V,GODLEVSKII L S.Superoxide dismutase and catalase activities in the retina during experimental diabetes and electric stimulation of the paleocerebellar cortex[J].Bull Exp Biol Med,2014,158(2):206-208.
[18] HO P D,PIL S J,TAEK K I.Association of plasma malondialdehyde with ARMS2 genetic variants and phenotypes in polypoidal choroidal vasculopathy and age-related macular degeneration[J].Retina,2014,34(6):1167-1176.
[19] ZHAO H L,WANG R Q,WU M Q,JIANG J.Dynamic changes of ocular biometric parameters:a modified form-deprivation myopia model of young guinea pigs[J].Int J Ophthalmol,2011,4(5):484-488.