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眼内钙化二醇:揭示维生素 D 在眼睛中的作用。

Intraocular calcidiol: Uncovering a role for vitamin D in the eye.

机构信息

Queen's University, Department of Ophthalmology, Kingston, Ontario, Canada.

Queen's University, Department of Biomedical and Molecular Sciences, Kingston, Ontario, Canada.

出版信息

J Steroid Biochem Mol Biol. 2020 Mar;197:105536. doi: 10.1016/j.jsbmb.2019.105536. Epub 2019 Nov 14.

Abstract

UNLABELLED

Vitamin D has emerged as a potentially important molecule in ophthalmology. To date, all ophthalmic data pertaining to vitamin D has been restricted primarily to tear and serum analysis in human patients. Considering the isolated nature of the eye, we sought to determine the presence of intraocular vitamin D in ocular disease.

METHODS

25-Hydroxyvitamin D (25(OH)D) concentrations were measured in the eye and blood of 120 participants undergoing ophthalmic procedures. Ocular localization of the 1,25-dihydroxyvitamin D-generating (CYP27B1) and deactivating (CYP24A1) hydroxylases was performed by immunohistochemistry. Gene expression of CYP27B1, CYP24A1 and VEGF-A was measured in eyes from patients with and without disease.

RESULTS

25(OH)D was quantified in 112 ocular samples. In 40 cataract patient samples, the average 25(OH)D concentration was 0.057 ng/mL, compared to 72 retinal disease patient samples, average of 0.502 ng/mL (p < 0.001). Intraocular 25(OH)D did not correlate with serum levels of 25(OH)D. There was no difference between the level of 25(OH)D measured in the aqueous and vitreous humour. The vitamin D-specific CYPs 27B1 and 24A1, strongly localized to complementary regions of the ciliary body, retinal pigment epithelium and neural retina. Gene expression analysis confirmed retinal CYP27B1 correlated strongly with VEGF-A in eyes from diabetic patients (r = 0.92, p < 0.001).

CONCLUSIONS

Our data confirms that vitamin D is present in the humours of the human eye and that local synthesis/degradation is possible via the ocular CYP27B1 and CYP24A1. This argues for a functional role for local vitamin D production and signaling in the eye and suggests that vitamin D may be an important intraocular mediator in disease pathogenesis.

摘要

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维生素 D 已成为眼科学中一种重要的潜在分子。迄今为止,所有与维生素 D 相关的眼科数据主要局限于人类患者的泪液和血清分析。考虑到眼睛的孤立性质,我们试图确定眼部疾病中是否存在眼内维生素 D。

方法

对 120 名接受眼科手术的患者的眼部和血液进行 25-羟维生素 D(25(OH)D)浓度测量。通过免疫组织化学法对 1,25-二羟维生素 D 生成(CYP27B1)和失活(CYP24A1)羟化酶进行眼部定位。测量无病和有病患者眼部 CYP27B1、CYP24A1 和 VEGF-A 的基因表达。

结果

在 112 个眼部样本中定量了 25(OH)D。在 40 例白内障患者样本中,25(OH)D 的平均浓度为 0.057ng/ml,而在 72 例视网膜疾病患者样本中,平均浓度为 0.502ng/ml(p<0.001)。眼内 25(OH)D 与血清 25(OH)D 水平无相关性。在房水和玻璃体中测量的 25(OH)D 水平没有差异。维生素 D 特异性 CYP27B1 和 24A1 强烈定位于睫状体、视网膜色素上皮和神经视网膜的互补区域。基因表达分析证实,糖尿病患者眼中的视网膜 CYP27B1 与 VEGF-A 呈强相关(r=0.92,p<0.001)。

结论

我们的数据证实,维生素 D 存在于人眼的房水中,通过眼 CYP27B1 和 CYP24A1 可以进行局部合成/降解。这表明局部维生素 D 产生和信号传递在眼睛中具有功能作用,并表明维生素 D 可能是疾病发病机制中的一种重要眼内介质。

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