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形觉剥夺性近视和离焦性近视在小鸡的多巴胺能系统药物干预下表现出相似的变化。

Form-Deprivation and Lens-Induced Myopia Are Similarly Affected by Pharmacological Manipulation of the Dopaminergic System in Chicks.

机构信息

Centre for Research in Therapeutic Solutions, Faculty of Science and Technology, University of Canberra, Canberra, Australia.

Research School of Biology, Australian National University, Canberra, Australia.

出版信息

Invest Ophthalmol Vis Sci. 2020 Oct 1;61(12):4. doi: 10.1167/iovs.61.12.4.

Abstract

PURPOSE

Animal models have demonstrated a link between decreases in retinal dopamine levels and the development of form-deprivation myopia (FDM). However, the consistency of dopamine's role in the other major form of experimental myopia, that of lens-induced myopia (LIM), is less clear, raising the question as to what extent dopamine plays a role in human myopia. Therefore, to better define the role of dopamine in both forms of experimental myopia, we examined how consistent the protection afforded by dopamine and the dopamine agonist 6-amino-5,6,7,8-tetrahydronaphthalene-2,3-diol hydrobromide (ADTN) is between FDM and LIM.

METHODS

Intravitreal injections of dopamine (0.002, 0.015, 0.150, 1.500 µmol) or ADTN (0.001, 0.010, 0.100, 1.000 µmol) were administered daily to chicks developing FDM or LIM. Axial length and refraction were measured following 4 days of treatment. To determine the receptor subtype by which dopamine and ADTN inhibit FDM and LIM, both compounds were coadministered with either the dopamine D2-like antagonist spiperone (0.005 µmol) or the D1-like antagonist SCH-23390 (0.005 µmol).

RESULTS

Intravitreal administration of dopamine or ADTN inhibited the development of FDM (ED50 = 0.003 µmol and ED50 = 0.011 µmol, respectively) and LIM (ED50 = 0.002 µmol and ED50 = 0.010 µmol, respectively) in a dose-dependent manner, with a similar degree of protection observed in both paradigms (P = 0.471 and P = 0.969, respectively). Coadministration with spiperone, but not SCH-23390, inhibited the protective effects of dopamine and ADTN against the development of both FDM (P = 0.214 and P = 0.138, respectively) and LIM (P = 0.116 and P = 0.100, respectively).

CONCLUSIONS

pharmacological targeting of the retinal dopamine system inhibits FDM and LIM in a similar dose-dependent manner through a D2-like mechanism.

摘要

目的

动物模型表明,视网膜多巴胺水平的降低与形觉剥夺性近视(FDM)的发展有关。然而,多巴胺在另一种主要形式的实验性近视,即晶状体诱导性近视(LIM)中的作用一致性尚不清楚,这引发了一个问题,即多巴胺在多大程度上参与了人类近视的发生。因此,为了更好地确定多巴胺在这两种形式的实验性近视中的作用,我们研究了多巴胺和多巴胺激动剂 6-氨基-5,6,7,8-四氢萘-2,3-二醇氢溴酸盐(ADTN)提供的保护在 FDM 和 LIM 之间是否一致。

方法

向发展 FDM 或 LIM 的小鸡眼内注射多巴胺(0.002、0.015、0.150、1.500µmol)或 ADTN(0.001、0.010、0.100、1.000µmol),每天一次。治疗 4 天后测量眼轴长度和屈光度。为了确定多巴胺和 ADTN 通过何种受体亚型抑制 FDM 和 LIM,我们将这两种化合物与多巴胺 D2 样拮抗剂哌泊噻嗪(0.005µmol)或 D1 样拮抗剂 SCH-23390(0.005µmol)共同给药。

结果

多巴胺或 ADTN 的眼内给药以剂量依赖性方式抑制 FDM(ED50=0.003µmol 和 ED50=0.011µmol)和 LIM(ED50=0.002µmol 和 ED50=0.010µmol)的发展,两种范式中观察到的保护程度相似(P=0.471 和 P=0.969,分别)。哌泊噻嗪的共同给药,但不是 SCH-23390,抑制了多巴胺和 ADTN 对 FDM(P=0.214 和 P=0.138,分别)和 LIM(P=0.116 和 P=0.100,分别)发展的保护作用。

结论

视网膜多巴胺系统的药理学靶向以类似的剂量依赖性方式通过 D2 样机制抑制 FDM 和 LIM。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02d4/7545069/af244af8bb38/iovs-61-12-4-f001.jpg

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