视黄酸信号传递元件在豚鼠离焦型近视中的作用
|
摘要
目的
建立豚鼠镜片诱导型近视眼模型(Lens induced myopia, LIM),观察豚鼠眼球后极部视网膜、脉络膜及巩膜中视黄酸(RA)、视黄酸受体β(RAR-β)和光感受器间维生素A类结合蛋白(IRBP)的表达变化,探讨视黄酸信号传递系统在豚鼠离焦型近视发生发展中的作用机制。
方法
3～4周龄花色豚鼠65只随机分成3组,空白对照组13只(26个眼,n=26),离焦Ⅰ组和离焦Ⅱ组各26只(n=26)。空白对照组双眼不做任何处理,离焦Ⅰ组和Ⅱ组豚鼠左眼不戴镜作为自身对照眼,右眼戴-10.00D凹透镜,分别戴镜14d、28d后除去镜片,测量豚鼠戴镜前和戴镜后双眼屈光度及眼轴长度。经检影验光及测定眼轴长度后,深度麻醉处死动物,摘除眼球,取后极部视网膜、脉络膜及巩膜,光镜下对比观察离焦型近视眼和对照眼视网膜的形态学变化;采用免疫组织化学法和Western blot技术检测视网膜中光感受器间维生素A类结合蛋白(IRBP)和视网膜、脉络膜及巩膜中视黄酸核受体β(RAR-β)的蛋白质的表达变化;用逆转录-多聚酶链反应(RT-PCR)法检测视网膜中IRBP及视网膜、脉络膜和巩膜中RAR-β的mRNA表达变化;应用高效液相色谱法(HPLC)检测视网膜、脉络膜和巩膜中的视黄酸(RA)含量。
结果
与自身对照眼及空白对照组相比较,Ⅰ组和Ⅱ组离焦眼形成明显的近视眼、眼轴延长(P<0.05),离焦Ⅱ组近视程度重于Ⅰ组(P<0.05)。视网膜HE染色及厚度测量可见,Ⅰ组和Ⅱ组离焦眼视网膜有核细胞数减少,视网膜变薄(P<0.05),但Ⅱ组离焦眼视网膜全层厚度及视网膜各层形态学改变与Ⅰ组离焦眼相比较差异无统计学意义(P>0.05)。与空白对照组和离焦组左眼相比,Ⅰ组和Ⅱ组右眼视网膜的IRBP蛋白及mRNA表达明显降低(P<0.05),Ⅱ组IRBP mRNA的表达量显著低于Ⅰ组(P<0.05)。与空白对照组和离焦组左眼相比,RAR-β蛋白及mRNA表达量在Ⅰ组和Ⅱ组右眼视网膜中明显增高(P<0.05),且离焦Ⅱ组比Ⅰ组RAR-β表达强(P<0.05);而在Ⅰ组和Ⅱ组右眼脉络膜及巩膜中明显下降(P<0.05),且Ⅱ组比Ⅰ组表达少(P<0.05)。视黄酸(RA)含量在离焦Ⅰ组和Ⅱ组视网膜、脉络膜和巩膜中均升高(P<0.05),Ⅰ组右眼视网膜、脉络膜及巩膜平均RA含量与Ⅱ组相比较差异无统计学意义(P>0.05)。
结论
1.幼龄豚鼠配戴-10D自制凹透镜可诱导形成明显的近视眼,配戴以kt板为镜框的自制近视镜可作为一种有效的离焦方法。
2.视黄酸(RA)在豚鼠视网膜、脉络膜及巩膜中均有表达,其中脉络膜含量最高。镜片离焦所致视环境改变后,视网膜、脉络膜及巩膜中的RA表达升高,提示RA参与了豚鼠离焦型近视的形成。
3.视黄酸受体β的表达在离焦型近视眼视网膜中增高,而在脉络膜及巩膜中下降,RAR-β的变化方向与近视程度发展一致,提示RAR-β可能参与了离焦型近视眼的形成和发展,RAR-β在离焦型近视眼中的作用机制与形觉剥夺型近视眼不同,可能与中枢调节有关。
4.视黄酸转运载体光感受器间维生素A类结合蛋白(IRBP)在离焦型近视眼视网膜中的表达减少,说明IRBP可能参与离焦型近视眼的发生发展,IRBP可能通过视觉中枢途径参与近视的形成。
Objective
To observe the effort of retinoic acid(RA) signal transport system components on lens induced myopia in guinea pig, investigate the level of RA and the expression of retinoic acid receptor-β(RAR-β) and the interphotoreceptor retinoid-binding protein(IRBP) in retina, choroid and sclera of guinea pigs in order to better understand the mechanism by which RA regulates myopia.
Methods
Sixty-five guinea pigs were randomized into the normal controls(26 eyes, n=26), defocusⅠgroup(n=26) and defocusⅡg roup(n=26). Guinea pigs in the defocus groups wore -10.00D lenses on the right eyes: defocusⅠgroup, wore lens 14d, and defocusⅡ, treated eyes 28d. The left eyes were not worn lenses as self-control. The refraction and axial length were measured before and after wearing lenses respectively. Light microscope was used to observe the changes of the retina. The protein expression of IRBP and RAR-βwas detected by immunohistochemisty and western blot. RT-PCR was used to observe the level of IRBP and RAR-βmRNA. The level of RA in retina, choroid and sclera was detected by high performance liquid chromatography (HPLC).
Results
Comparing with the control eyes, the lens-worn eyes of defocusⅠandⅡg roups became myopic and elongated(P<0.05, respectively) and the degree of defocusⅡg roup outweigh that of defocusⅠgroup. The thickness of retina in defocus eyes decreased and the number of retina cells reduced(P<0.05). The level of RA in retina, choroid and sclera was significantly set-up(P<0.05) ,and the two defocus groups have no statistic defferences(P>0.05). The protein expression and the mRNA level of IRBP and was significantly lower(P<0.05) in the treated eyes relative to control eyes, especially in defocusⅡgroup. The protein expression and the mRNA level of RAR-βin retina of the defocus groups increased significantly (P<0.05), while decreased significantly in choroid and sclera(P<0.05).
Conclusion
1.-10D lens wearing can induce guinea pigs to form myopia, and self-made lens with kt board frame for myopia can be used as an effective defocus method.
2.Retinoic acid(RA) were expressed in retina, choroid and sclera of guinea pig, of which the choroid content highest. RA expression significant increased when the visual environment changed by lens defocus, suggesting that RA may take part in the formation of Lens Induced Myopia.
3. The expression of retinoic acid receptor (RAR-β) increased in retina, while decreased in choroid and sclera of guinea pig with Lens Induced Myopia. The direction of RAR-βchanges consistent with the development of myopia, suggesting that RAR-βmay be involved in the formation and development of Lens Induced Myopia. The mechanism of RAR-βin Lens Induced Myopia may be related to optic centre.
4.The expression of the interphotoreceptor retinoid-binding protein(IRBP) in retina in defocus eyes decreased, indicating that IRBP may be take a part in the formation and development of Lens Induced Myopia and IRBP may participate by means of visual centre.
建立豚鼠镜片诱导型近视眼模型(Lens induced myopia, LIM),观察豚鼠眼球后极部视网膜、脉络膜及巩膜中视黄酸(RA)、视黄酸受体β(RAR-β)和光感受器间维生素A类结合蛋白(IRBP)的表达变化,探讨视黄酸信号传递系统在豚鼠离焦型近视发生发展中的作用机制。
方法
3～4周龄花色豚鼠65只随机分成3组,空白对照组13只(26个眼,n=26),离焦Ⅰ组和离焦Ⅱ组各26只(n=26)。空白对照组双眼不做任何处理,离焦Ⅰ组和Ⅱ组豚鼠左眼不戴镜作为自身对照眼,右眼戴-10.00D凹透镜,分别戴镜14d、28d后除去镜片,测量豚鼠戴镜前和戴镜后双眼屈光度及眼轴长度。经检影验光及测定眼轴长度后,深度麻醉处死动物,摘除眼球,取后极部视网膜、脉络膜及巩膜,光镜下对比观察离焦型近视眼和对照眼视网膜的形态学变化;采用免疫组织化学法和Western blot技术检测视网膜中光感受器间维生素A类结合蛋白(IRBP)和视网膜、脉络膜及巩膜中视黄酸核受体β(RAR-β)的蛋白质的表达变化;用逆转录-多聚酶链反应(RT-PCR)法检测视网膜中IRBP及视网膜、脉络膜和巩膜中RAR-β的mRNA表达变化;应用高效液相色谱法(HPLC)检测视网膜、脉络膜和巩膜中的视黄酸(RA)含量。
结果
与自身对照眼及空白对照组相比较,Ⅰ组和Ⅱ组离焦眼形成明显的近视眼、眼轴延长(P<0.05),离焦Ⅱ组近视程度重于Ⅰ组(P<0.05)。视网膜HE染色及厚度测量可见,Ⅰ组和Ⅱ组离焦眼视网膜有核细胞数减少,视网膜变薄(P<0.05),但Ⅱ组离焦眼视网膜全层厚度及视网膜各层形态学改变与Ⅰ组离焦眼相比较差异无统计学意义(P>0.05)。与空白对照组和离焦组左眼相比,Ⅰ组和Ⅱ组右眼视网膜的IRBP蛋白及mRNA表达明显降低(P<0.05),Ⅱ组IRBP mRNA的表达量显著低于Ⅰ组(P<0.05)。与空白对照组和离焦组左眼相比,RAR-β蛋白及mRNA表达量在Ⅰ组和Ⅱ组右眼视网膜中明显增高(P<0.05),且离焦Ⅱ组比Ⅰ组RAR-β表达强(P<0.05);而在Ⅰ组和Ⅱ组右眼脉络膜及巩膜中明显下降(P<0.05),且Ⅱ组比Ⅰ组表达少(P<0.05)。视黄酸(RA)含量在离焦Ⅰ组和Ⅱ组视网膜、脉络膜和巩膜中均升高(P<0.05),Ⅰ组右眼视网膜、脉络膜及巩膜平均RA含量与Ⅱ组相比较差异无统计学意义(P>0.05)。
结论
1.幼龄豚鼠配戴-10D自制凹透镜可诱导形成明显的近视眼,配戴以kt板为镜框的自制近视镜可作为一种有效的离焦方法。
2.视黄酸(RA)在豚鼠视网膜、脉络膜及巩膜中均有表达,其中脉络膜含量最高。镜片离焦所致视环境改变后,视网膜、脉络膜及巩膜中的RA表达升高,提示RA参与了豚鼠离焦型近视的形成。
3.视黄酸受体β的表达在离焦型近视眼视网膜中增高,而在脉络膜及巩膜中下降,RAR-β的变化方向与近视程度发展一致,提示RAR-β可能参与了离焦型近视眼的形成和发展,RAR-β在离焦型近视眼中的作用机制与形觉剥夺型近视眼不同,可能与中枢调节有关。
4.视黄酸转运载体光感受器间维生素A类结合蛋白(IRBP)在离焦型近视眼视网膜中的表达减少,说明IRBP可能参与离焦型近视眼的发生发展,IRBP可能通过视觉中枢途径参与近视的形成。
Objective
To observe the effort of retinoic acid(RA) signal transport system components on lens induced myopia in guinea pig, investigate the level of RA and the expression of retinoic acid receptor-β(RAR-β) and the interphotoreceptor retinoid-binding protein(IRBP) in retina, choroid and sclera of guinea pigs in order to better understand the mechanism by which RA regulates myopia.
Methods
Sixty-five guinea pigs were randomized into the normal controls(26 eyes, n=26), defocusⅠgroup(n=26) and defocusⅡg roup(n=26). Guinea pigs in the defocus groups wore -10.00D lenses on the right eyes: defocusⅠgroup, wore lens 14d, and defocusⅡ, treated eyes 28d. The left eyes were not worn lenses as self-control. The refraction and axial length were measured before and after wearing lenses respectively. Light microscope was used to observe the changes of the retina. The protein expression of IRBP and RAR-βwas detected by immunohistochemisty and western blot. RT-PCR was used to observe the level of IRBP and RAR-βmRNA. The level of RA in retina, choroid and sclera was detected by high performance liquid chromatography (HPLC).
Results
Comparing with the control eyes, the lens-worn eyes of defocusⅠandⅡg roups became myopic and elongated(P<0.05, respectively) and the degree of defocusⅡg roup outweigh that of defocusⅠgroup. The thickness of retina in defocus eyes decreased and the number of retina cells reduced(P<0.05). The level of RA in retina, choroid and sclera was significantly set-up(P<0.05) ,and the two defocus groups have no statistic defferences(P>0.05). The protein expression and the mRNA level of IRBP and was significantly lower(P<0.05) in the treated eyes relative to control eyes, especially in defocusⅡgroup. The protein expression and the mRNA level of RAR-βin retina of the defocus groups increased significantly (P<0.05), while decreased significantly in choroid and sclera(P<0.05).
Conclusion
1.-10D lens wearing can induce guinea pigs to form myopia, and self-made lens with kt board frame for myopia can be used as an effective defocus method.
2.Retinoic acid(RA) were expressed in retina, choroid and sclera of guinea pig, of which the choroid content highest. RA expression significant increased when the visual environment changed by lens defocus, suggesting that RA may take part in the formation of Lens Induced Myopia.
3. The expression of retinoic acid receptor (RAR-β) increased in retina, while decreased in choroid and sclera of guinea pig with Lens Induced Myopia. The direction of RAR-βchanges consistent with the development of myopia, suggesting that RAR-βmay be involved in the formation and development of Lens Induced Myopia. The mechanism of RAR-βin Lens Induced Myopia may be related to optic centre.
4.The expression of the interphotoreceptor retinoid-binding protein(IRBP) in retina in defocus eyes decreased, indicating that IRBP may be take a part in the formation and development of Lens Induced Myopia and IRBP may participate by means of visual centre.
引文
1吴君舒,钟兴武,聂昊辉,等.光学离焦和形觉剥夺对幼恒河猴正视化过程的影响.眼科学报,2004,20(2):118-122.
2许军,赵江月,王洪学,等.形觉剥夺下雏鸡视网膜、脉络膜和巩膜中全反视黄酸含量的变化.国际眼科杂志,2007,7(3):677-681.
3 Troilo D, Nickla DL, Mertz JR, et al. Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets. Invest Ophthalmol Vis Sci, 2006, 47(5):1768-1777.
4吕勇,张金嵩,闫磐石,等.RAR-β在豚鼠形觉剥夺性近视眼中的表达.眼科研究,2006,24(4):411-414.
5许军,陆博,马立威,等.形觉剥夺下雏鸡后极部巩膜中MMP-2 /TIMP-2及RARβ表达变化.中国实用眼科杂志,2010,28(1):84-89.
6史剑波,徐锦堂,夏潮涌,等.豚鼠视网膜正常结构的定量研究.眼科研究,1999,17(2):98-100.
7 Howlett MH, McFadden SA. Spectacle lens compensation in the pigmented guinea pig. Vision Res, 2009,49(2):219-227.
8 Howlett MH, McFadden SA. Emmetropization and schematic eye models in developing pigmented guinea pigs. Vision Res, 2007,47(9):1178-1190.
9欧阳朝祜,胡文政,褚仁远.凹透镜对豚鼠眼生长及屈光发展的影响.眼科研究,2002,20(5):391-393.
10 Bitzer M, Feldkaemper M, Schaeffel F. Visually induced changes in components of the retinoic acid system in fundal layers of the chick. Exp Eye Res 2000, 70(1):97-106.
11王剑峰,刘双珍,吴文灿.外源性视黄酸对鸡后巩膜基质MMP-2/TIMP-2表达作用的动态观察.眼科研究,2005,23(6):596-599.
12崔冬梅,高岩,任亚林,等.全反式视黄酸对体外培养人巩膜成纤维细胞的抑制作用.国际眼科杂志,2008,8(12):2397-2400.
13李瑾,褚仁远,瞿小妹,等.全反视黄酸(ATRA)对培养的人视网膜色素上皮细胞的影响.眼视光杂志,2007,9(2):73-76.
14 Rohrer B, Stell WK. Basic fibroblast growth factor(bFGF)and transforming growth factor beta(TGF-beta) act as stop and go signals to modulate postnatal ocular growth in the chick. Exp Eye Res, 1994,58(5):553-561.
15许军,赵江月,王洪学,等.形觉剥夺下雏鸡视网膜、脉络膜和巩膜中全反视黄酸含量的变化.国际眼科杂志,2007,7(3):677-681.
16 McFadden SA, Howlett MH, Mertz JR. Retinoic acid signals the direction of ocular elongation in the guinea pig eye. Vision Res, 2004,44(7):643-653.
17赵小云,黄悦,赵少贞.视黄酸在早期形觉剥夺性近视豚鼠后巩膜中的变化.眼科研究,2009,27(12):1115-1119.
18 Liao WL, Wang HF, Tsai HC, et al. Retinoid signaling competence and RARbeta-mediated gene regulation in the developing mammalian telencephalon. Dev Dyn, 2005,232(4):887-900.
19 Zhou G, Strom RC, Giguere V, et al. Modulation of retinal cell populations and eye size in retinoic receptor knockout mice. Mol Vis, 2001,7:253-260.
20 Seko Y, Shimokawa H, Tokoro T. In vivo and in vitro association of retinoic acid with form- deprivation myopia in the chick. Exp Eye Res, 1996,63(4):443-452.
21崔冬梅,聂玉红,高岩,等.胞内视黄醛结合蛋白在豚鼠离焦诱导型近视眼中的表达.眼科研究,2009,27(2):91-94.
22黄佳,瞿小妹,褚仁远.豚鼠形觉剥夺性近视视网膜中视黄酸系统的研究[J].眼科研究,2009,27(11):1006-1010.
23杨培增,李绍珍,毛文书,等.光感受器间维生素A类结合蛋白诱发的色素膜视网膜炎和松果体炎.中华眼科杂志,1993,29(6):373-376.
24 Jin M, Li S, Nusinowitz S, Lloyd M, et al. The role of interphotoreceptor retinoid-binding protein on the translocation of visual retinoids and function of cone photoreceptors. J Neurosci, 2009,29(5):1486-1495.
25陈冬红,褚仁远,周国民,等.不同波长有色光对豚鼠眼球生长发育的影响.眼视光学杂志,2003,5(3):144-146.
1许军,赵江月,王洪学,等.形觉剥夺下雏鸡视网膜、脉络膜和巩膜中全反视黄酸含量的变化.国际眼科杂志,2007,7(3):677-681.
2 Wirtanen L, Séguin C. Cloning of cDNAs encoding retinoic acid receptors RAR gamma 1, RAR gamma 2, and a new splicing variant, RAR gamma 3, from Aambystoma mexicanum and characterization of their expression during early development. Biochim Biophys Acta, 2000, 1492(1):81-93.
3闫东升,周翔天,陈晓燕,等.人眼巩膜成纤维细胞中视黄酸受体的分布及其对巩膜成纤维细胞的生长控制.中华眼科杂志,2007,43(8):750-753.
4吕勇,张金蒿,闫磐石,等.RARβ在豚鼠形觉剥夺性近视眼中的表达.眼科研究,2006,24(4):411-414.
5 Veerappan S, Schache M, Pertile KK, et al. The retinoic acid receptor alpha(RARA) gene is not associated with myopia, hypermetropia, and ocular biometric measures. Mol Vis, 2009, 15:1390-1397.
6王悦,李俊.视黄酸与实验性近视关系的研究进展.国际眼科杂志,2008,8(8):1654-1656.
7钟兴武,葛坚,陈晓莲,等.猴光学离焦性与形觉剥夺性近视眼视网膜形态及超微结构比较.中华眼科杂志,2005,41(7):625-630.
8 Bitzer M, Feldkaemper M, Schaeffel F. Visually induced changes in components of the retinoic acid system in fundal layers of the chick. Exp Eye Res, 2000, 70(1):97-106.
9王嫒,张金蒿,王艳婷,等.全反视黄酸对兔视网膜色素上皮细胞的影响.眼科研究,2009,27(5):397-400.
10李瑾,褚仁远,瞿小妹,等.全反视黄酸对培养的人视网膜色素上皮细胞的影响.眼视光学杂志,2007,9(2):73-76,79.
11谢芳,陈跃国.双硫仑对鸡形觉剥夺性近视眼中转化生长因子-β2表达的影响.北京大学学报(医学版),2008,40(6):610-615.
12张艳莉,聂玉红,许洁娜,等.全反式视黄酸对体外培养大鼠Müller细胞生长的影响.眼科学报,2007,23(3):163-167.
13陈冬红,褚仁远,周国民,等.不同波长有色光对豚鼠眼球生长发育的影响.眼视光学杂志,2003,5(3):144-146.
14 Kroger RH, Wagner HJ. The eye of the blue acara (Aequidens pulcher, Cichlidae) grows to compensate for defocus due to chromatic aberration. J Comp Physiol A, 1996,179(6):837-842.
15 Prabhudesai SN, Cameron DA, Stenkamp DL. Targeted effects of retinoic acid signaling upon photoreceptor development in zebrafish. Dev Biol, 2005, 287(1):157-167.
16李瑾,褚仁远,赵云娥.外源性全反视黄酸对出生后豚鼠锥细胞视蛋白表达和方向的影响.眼视光学杂志,2008,10(4):273-276.
17胡敏,钟华,刘永松,等.形觉剥夺性和光学离焦性近视豚鼠视紫红质表达变化研究.眼科学报,2008,24(1):1-5.
18 Mertz JR, Wallman J. Choroidal retinoic acid synthesis: a possible mediator between refractive error and compensatory eye growth. Exp Eye Res, 2000, 70(4):519-527.
19 Troilo D, Nickla DL, Mertz JR, et al. Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets. Invest Ophthalmol Vis Sci, 2006, 47(5):1768-1777.
20 Rada JAS, Wiechmann AF. Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation. Invest Ophthalmol Vis Sci, 2006, 47(1):25-33.
21蒋莉,刘双珍,王剑峰.视黄酸对体外培养的鸡巩膜成纤维细胞MMP-2表达的影响.国际眼科杂志,2004,4(5):824-828.
22王剑峰,刘双珍,吴文灿.外源性视黄酸对鸡后巩膜基质MMP-2/TIMP-2表达作用的动态观察.眼科研究,2005,23(6):596-599.
23崔冬梅,高岩,任亚林,等.全反式视黄酸对体外培养人巩膜成纤维细胞的抑制作用.国际眼科杂志,2008,8(12):2397-2400.
24闫东升,周翔天,陈晓燕,等.人眼巩膜成纤维细胞中视黄酸受体的分布及其对巩膜成纤维细胞的生长控制.中华眼科杂志,2007,43(8):750-753.
25刘双珍,蒋莉,王剑峰.视黄酸对培养的鸡巩膜成纤维细胞增殖及超微结构的影响.国际眼科杂志,2005,5(1):62-65.
2许军,赵江月,王洪学,等.形觉剥夺下雏鸡视网膜、脉络膜和巩膜中全反视黄酸含量的变化.国际眼科杂志,2007,7(3):677-681.
3 Troilo D, Nickla DL, Mertz JR, et al. Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets. Invest Ophthalmol Vis Sci, 2006, 47(5):1768-1777.
4吕勇,张金嵩,闫磐石,等.RAR-β在豚鼠形觉剥夺性近视眼中的表达.眼科研究,2006,24(4):411-414.
5许军,陆博,马立威,等.形觉剥夺下雏鸡后极部巩膜中MMP-2 /TIMP-2及RARβ表达变化.中国实用眼科杂志,2010,28(1):84-89.
6史剑波,徐锦堂,夏潮涌,等.豚鼠视网膜正常结构的定量研究.眼科研究,1999,17(2):98-100.
7 Howlett MH, McFadden SA. Spectacle lens compensation in the pigmented guinea pig. Vision Res, 2009,49(2):219-227.
8 Howlett MH, McFadden SA. Emmetropization and schematic eye models in developing pigmented guinea pigs. Vision Res, 2007,47(9):1178-1190.
9欧阳朝祜,胡文政,褚仁远.凹透镜对豚鼠眼生长及屈光发展的影响.眼科研究,2002,20(5):391-393.
10 Bitzer M, Feldkaemper M, Schaeffel F. Visually induced changes in components of the retinoic acid system in fundal layers of the chick. Exp Eye Res 2000, 70(1):97-106.
11王剑峰,刘双珍,吴文灿.外源性视黄酸对鸡后巩膜基质MMP-2/TIMP-2表达作用的动态观察.眼科研究,2005,23(6):596-599.
12崔冬梅,高岩,任亚林,等.全反式视黄酸对体外培养人巩膜成纤维细胞的抑制作用.国际眼科杂志,2008,8(12):2397-2400.
13李瑾,褚仁远,瞿小妹,等.全反视黄酸(ATRA)对培养的人视网膜色素上皮细胞的影响.眼视光杂志,2007,9(2):73-76.
14 Rohrer B, Stell WK. Basic fibroblast growth factor(bFGF)and transforming growth factor beta(TGF-beta) act as stop and go signals to modulate postnatal ocular growth in the chick. Exp Eye Res, 1994,58(5):553-561.
15许军,赵江月,王洪学,等.形觉剥夺下雏鸡视网膜、脉络膜和巩膜中全反视黄酸含量的变化.国际眼科杂志,2007,7(3):677-681.
16 McFadden SA, Howlett MH, Mertz JR. Retinoic acid signals the direction of ocular elongation in the guinea pig eye. Vision Res, 2004,44(7):643-653.
17赵小云,黄悦,赵少贞.视黄酸在早期形觉剥夺性近视豚鼠后巩膜中的变化.眼科研究,2009,27(12):1115-1119.
18 Liao WL, Wang HF, Tsai HC, et al. Retinoid signaling competence and RARbeta-mediated gene regulation in the developing mammalian telencephalon. Dev Dyn, 2005,232(4):887-900.
19 Zhou G, Strom RC, Giguere V, et al. Modulation of retinal cell populations and eye size in retinoic receptor knockout mice. Mol Vis, 2001,7:253-260.
20 Seko Y, Shimokawa H, Tokoro T. In vivo and in vitro association of retinoic acid with form- deprivation myopia in the chick. Exp Eye Res, 1996,63(4):443-452.
21崔冬梅,聂玉红,高岩,等.胞内视黄醛结合蛋白在豚鼠离焦诱导型近视眼中的表达.眼科研究,2009,27(2):91-94.
22黄佳,瞿小妹,褚仁远.豚鼠形觉剥夺性近视视网膜中视黄酸系统的研究[J].眼科研究,2009,27(11):1006-1010.
23杨培增,李绍珍,毛文书,等.光感受器间维生素A类结合蛋白诱发的色素膜视网膜炎和松果体炎.中华眼科杂志,1993,29(6):373-376.
24 Jin M, Li S, Nusinowitz S, Lloyd M, et al. The role of interphotoreceptor retinoid-binding protein on the translocation of visual retinoids and function of cone photoreceptors. J Neurosci, 2009,29(5):1486-1495.
25陈冬红,褚仁远,周国民,等.不同波长有色光对豚鼠眼球生长发育的影响.眼视光学杂志,2003,5(3):144-146.
1许军,赵江月,王洪学,等.形觉剥夺下雏鸡视网膜、脉络膜和巩膜中全反视黄酸含量的变化.国际眼科杂志,2007,7(3):677-681.
2 Wirtanen L, Séguin C. Cloning of cDNAs encoding retinoic acid receptors RAR gamma 1, RAR gamma 2, and a new splicing variant, RAR gamma 3, from Aambystoma mexicanum and characterization of their expression during early development. Biochim Biophys Acta, 2000, 1492(1):81-93.
3闫东升,周翔天,陈晓燕,等.人眼巩膜成纤维细胞中视黄酸受体的分布及其对巩膜成纤维细胞的生长控制.中华眼科杂志,2007,43(8):750-753.
4吕勇,张金蒿,闫磐石,等.RARβ在豚鼠形觉剥夺性近视眼中的表达.眼科研究,2006,24(4):411-414.
5 Veerappan S, Schache M, Pertile KK, et al. The retinoic acid receptor alpha(RARA) gene is not associated with myopia, hypermetropia, and ocular biometric measures. Mol Vis, 2009, 15:1390-1397.
6王悦,李俊.视黄酸与实验性近视关系的研究进展.国际眼科杂志,2008,8(8):1654-1656.
7钟兴武,葛坚,陈晓莲,等.猴光学离焦性与形觉剥夺性近视眼视网膜形态及超微结构比较.中华眼科杂志,2005,41(7):625-630.
8 Bitzer M, Feldkaemper M, Schaeffel F. Visually induced changes in components of the retinoic acid system in fundal layers of the chick. Exp Eye Res, 2000, 70(1):97-106.
9王嫒,张金蒿,王艳婷,等.全反视黄酸对兔视网膜色素上皮细胞的影响.眼科研究,2009,27(5):397-400.
10李瑾,褚仁远,瞿小妹,等.全反视黄酸对培养的人视网膜色素上皮细胞的影响.眼视光学杂志,2007,9(2):73-76,79.
11谢芳,陈跃国.双硫仑对鸡形觉剥夺性近视眼中转化生长因子-β2表达的影响.北京大学学报(医学版),2008,40(6):610-615.
12张艳莉,聂玉红,许洁娜,等.全反式视黄酸对体外培养大鼠Müller细胞生长的影响.眼科学报,2007,23(3):163-167.
13陈冬红,褚仁远,周国民,等.不同波长有色光对豚鼠眼球生长发育的影响.眼视光学杂志,2003,5(3):144-146.
14 Kroger RH, Wagner HJ. The eye of the blue acara (Aequidens pulcher, Cichlidae) grows to compensate for defocus due to chromatic aberration. J Comp Physiol A, 1996,179(6):837-842.
15 Prabhudesai SN, Cameron DA, Stenkamp DL. Targeted effects of retinoic acid signaling upon photoreceptor development in zebrafish. Dev Biol, 2005, 287(1):157-167.
16李瑾,褚仁远,赵云娥.外源性全反视黄酸对出生后豚鼠锥细胞视蛋白表达和方向的影响.眼视光学杂志,2008,10(4):273-276.
17胡敏,钟华,刘永松,等.形觉剥夺性和光学离焦性近视豚鼠视紫红质表达变化研究.眼科学报,2008,24(1):1-5.
18 Mertz JR, Wallman J. Choroidal retinoic acid synthesis: a possible mediator between refractive error and compensatory eye growth. Exp Eye Res, 2000, 70(4):519-527.
19 Troilo D, Nickla DL, Mertz JR, et al. Change in the synthesis rates of ocular retinoic acid and scleral glycosaminoglycan during experimentally altered eye growth in marmosets. Invest Ophthalmol Vis Sci, 2006, 47(5):1768-1777.
20 Rada JAS, Wiechmann AF. Melatonin receptors in chick ocular tissues: implications for a role of melatonin in ocular growth regulation. Invest Ophthalmol Vis Sci, 2006, 47(1):25-33.
21蒋莉,刘双珍,王剑峰.视黄酸对体外培养的鸡巩膜成纤维细胞MMP-2表达的影响.国际眼科杂志,2004,4(5):824-828.
22王剑峰,刘双珍,吴文灿.外源性视黄酸对鸡后巩膜基质MMP-2/TIMP-2表达作用的动态观察.眼科研究,2005,23(6):596-599.
23崔冬梅,高岩,任亚林,等.全反式视黄酸对体外培养人巩膜成纤维细胞的抑制作用.国际眼科杂志,2008,8(12):2397-2400.
24闫东升,周翔天,陈晓燕,等.人眼巩膜成纤维细胞中视黄酸受体的分布及其对巩膜成纤维细胞的生长控制.中华眼科杂志,2007,43(8):750-753.
25刘双珍,蒋莉,王剑峰.视黄酸对培养的鸡巩膜成纤维细胞增殖及超微结构的影响.国际眼科杂志,2005,5(1):62-65.