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[双硫仑对雏鸡形觉剥夺眼转化生长因子-β2表达的影响]

[Influence of disulfiram on the expression of transforming growth factor-beta2 in form-deprived eyes in chicks].

作者信息

Xie Fang, Chen Yue Guo

机构信息

Peking University Eye Center, Peking University Third Hospital, Beijing, China.

出版信息

Beijing Da Xue Xue Bao Yi Xue Ban. 2008 Dec 18;40(6):610-5.

PMID:19088833
Abstract

OBJECTIVE

To explore the temporal expression of retinal-choroidal transforming growth factor-beta2 (TGF-beta2) in form-deprived myopia (FDM) chick eyes and study the effect of an inhibitor (disulfiram, DSF) of retinoid acid (RA) synthesis on refractive development and the expression of TGF-beta2.

METHODS

Ninety new hatched white leghorn chicks were divided randomly and equally into 3 groups: unilateral occluded with frosted goggles (Group A); unilateral intravitreal injection of 4 mmol of the non-specific aldehydedehydrogenase inhibitor disulfiram with further treatment with goggles (Group B); unilateral intravitreal injections of 4 mmol of disulfiram without further treatment with goggles (Group C). Refraction and axial length were measured on 1, 7 and 14 days after treatment. Expression levels of TGF-beta2 and TGF-beta2 mRNA in the retinal-choroid layer were analyzed by immunohistochemistry and real-time RT-PCR.

RESULTS

In Group A, the form-deprived eyes made by goggles developed myopia (P<0.05 on day 1, P<0.01 on days 7 and 14, compared with the contralateral eyes) with a lengthening of the axial length (P<0.01 on days 7 and 14, compared with the contralateral eyes), as well as a lower level of TGF-beta2 expression (P<0.01 on days 7 and 14, compared with the contralateral eyes). In Groups B and C, there was no statistically significant difference in refraction and axial length between treated and contralateral eyes (P>0.05) with TGF-beta2 mRNA level growing on day 7 and decreased on day 14 in group B and decreased on day 1, increased on days 7 and 14 in Group C (P<0.01, compared with the contralateral eyes). Immunohistochemistry showed that the expression of TGF-beta2 was mainly changed in the outer part of photoreceptor layer and retinal pigment epithelium (RPE) layer.

CONCLUSION

TGF-beta2 mRNA level decreased in FDM eyes. Disulfiram can up-regulate the level of TGF-beta2 mRNA expression in the posterior retinal-choroid, and inhibit the elongation of axial length and refractive error made by frosted goggles as well. Disulfiram which inhibits the synthesis of retinoid acid may suppress deprivation myopia by up-regulating the expression level of TGF-beta2 mRNA.

摘要

目的

探讨形觉剥夺性近视(FDM)雏鸡眼中视网膜 - 脉络膜转化生长因子 - β2(TGF - β2)的时间表达情况,并研究维甲酸(RA)合成抑制剂(双硫仑,DSF)对屈光发育及TGF - β2表达的影响。

方法

将90只新孵出的白来航雏鸡随机等分为3组:单侧用磨砂眼罩遮盖(A组);单侧玻璃体腔内注射4 mmol非特异性醛脱氢酶抑制剂双硫仑并进一步用眼罩处理(B组);单侧玻璃体腔内注射4 mmol双硫仑且不进一步用眼罩处理(C组)。在处理后第1、7和14天测量屈光和眼轴长度。通过免疫组织化学和实时逆转录 - 聚合酶链反应(RT - PCR)分析视网膜 - 脉络膜层中TGF - β2和TGF - β2 mRNA的表达水平。

结果

在A组中,眼罩造成的形觉剥夺眼出现近视(与对侧眼相比,第1天P<0.05,第7天和第14天P<0.01),眼轴长度延长(与对侧眼相比,第7天和第14天P<0.01),同时TGF - β2表达水平降低(与对侧眼相比,第7天和第14天P<0.01)。在B组和C组中,处理眼与对侧眼在屈光和眼轴长度方面无统计学显著差异(P>0.05),B组中TGF - β2 mRNA水平在第7天升高,第14天降低;C组中第1天降低,第7天和第14天升高(与对侧眼相比,P<0.01)。免疫组织化学显示,TGF - β2的表达主要在光感受器层外部和视网膜色素上皮(RPE)层发生变化。

结论

FDM眼中TGF - β2 mRNA水平降低。双硫仑可上调视网膜 - 脉络膜后部TGF - β2 mRNA的表达水平,并抑制磨砂眼罩导致的眼轴长度延长和屈光不正。抑制维甲酸合成的双硫仑可能通过上调TGF - β2 mRNA的表达水平来抑制剥夺性近视。

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