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视网膜代谢谱在 IMPG2 缺乏症合并视网膜下病变的小鼠模型中的研究。

Retinal Metabolic Profile on IMPG2 Deficiency Mice with Subretinal Lesions.

机构信息

Departments of Biochemistry and molecular medicine, and Ophthalmology and Visual Sciences, West Virginia University, Morgantown, WV, USA.

出版信息

Adv Exp Med Biol. 2023;1415:457-463. doi: 10.1007/978-3-031-27681-1_67.

Abstract

The interphotoreceptor matrix (IPM) is the extracellular matrix between the photoreceptors and the retinal pigment epithelium (RPE). The IPM has two proteoglycans: the IPM proteoglycans 1 and 2 (IMPG1 and IMPG2, respectively). Patients with mutations on IMPG2 develop subretinal vitelliform lesions that affect vision. We previously created an IMPG2 knockout (KO) mice model that generates subretinal lesions similar to those found in humans. These subretinal lesions in IMPG2 KO mice retinas are, in part, composed of mislocalized IMPG1. In addition, IMPG2 KO mice show microscopic IMPG1 material accumulation between the RPE and the photoreceptor outer segments. In this work we discuss the possibility that material accumulation on IMPG2 KO mice retinas affects photoreceptor metabolism. To further investigate this idea, we used targeted metabolomics to profile retinal metabolome on IMPG2 KO mice. The metabolite set enrichment analysis showed reduced glutamate metabolism, urea cycle, and galactose metabolism suggesting affected energy metabolism in mice retinas of IMPG2 KO mice with subretinal lesion.

摘要

光感受器间基质 (IPM) 是光感受器和视网膜色素上皮 (RPE) 之间的细胞外基质。IPM 有两种蛋白聚糖:IPM 蛋白聚糖 1 和 2(分别为 IMPG1 和 IMPG2)。IMP G2 基因突变的患者会出现影响视力的视网膜下类卵黄质病变。我们之前创建了一个 IMPG2 敲除 (KO) 小鼠模型,该模型会产生类似于人类的视网膜下病变。这些 IMPG2 KO 小鼠视网膜中的视网膜下病变部分是由定位错误的 IMPG1 组成的。此外,IMPG2 KO 小鼠的 RPE 和光感受器外段之间有微小的 IMPG1 物质堆积。在这项工作中,我们讨论了视网膜下病变对 IMPG2 KO 小鼠的物质堆积是否会影响光感受器代谢的可能性。为了进一步研究这个想法,我们使用靶向代谢组学对 IMPG2 KO 小鼠的视网膜代谢组进行了分析。代谢物集富集分析显示,谷氨酸代谢、尿素循环和半乳糖代谢减少,表明 IMPG2 KO 小鼠的视网膜代谢受到影响。

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