Retinal Pigment Epithelium Specific Metabolic Phenotypes Are Regulated by High-Mobility Group Protein N1.

IF 5 2区医学 Q1 OPHTHALMOLOGY

Investigative ophthalmology & visual science Pub Date : 2025-04-01 DOI:10.1167/iovs.66.4.70

Toshiaki Abe, Reiko Daigaku, Xie Yuting, Yasukazu Daigaku, Nobuhiro Nagai, Hirokazu Kaji, Aya Katsuyama, Yuki Katsukura, Yasuko Izumida, Atsuko Suzuki, Shinji Yamada, Yao-Wen Chang, Keiko Terada, Sei-Ichi Ishiguro, Noriko Osumi, Hiroshi Kunikata, Toru Nakazawa

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引用次数: 0

Abstract

Purpose: The retinal pigment epithelium (RPE) performs life-long phagocytosis of lipid-rich photoreceptor outer segments and exchanges energy metabolites with photoreceptors to support retinal function. The metabolites of glucose and lipid metabolism are interconnected, but it is unclear how the specialized lipid metabolism of RPE and glucose metabolism are regulated. We have investigated this unique mechanism.

Methods: To identify factors involved in regulation of metabolism in RPE we compared and screened the human retinal pigment epithelial cell line, ARPE-19 under different conditions. Using the results of these experiments we selected the high-mobility group nucleosome-associated protein 1 (HMGN1) as a candidate and analyzed HMGN1 deleted ARPE-19 (HGMN1-/--ARPE-19) and Hmgn1 knock-out mice (Hmgn1-/- mice).

Results: HMGN1 was identified as being involved in energy metabolism via altered expression. HMGN1-/--ARPE-19 cells prefer fatty acid oxidation over glucose metabolism as an energy source. Hmgn1-/- mice had a lower lipid weight of epididymal fat mass and serum lipids than those of control on a standard diet and showed impaired glucose tolerance. The mice also showed retinal dysfunction, similar to that observed in aged control retina as measured by electroretinogram. However, a palmitate-rich diet, as well as RPE-specific HMGN1 re-expression mitigated retinal dysfunction. HMGN1 is specifically downregulated in the RPE/choroid with aging, which is reminiscent of age-related metabolic changes in RPE/choroid.

Conclusions: HMGN1 is involved in energy metabolism and its altered expression modulates RPE-specific metabolic phenotypes.

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视网膜色素上皮特异性代谢表型受高迁移率蛋白N1调控。

目的：视网膜色素上皮（RPE）终身吞噬富含脂质的光感受器外节，并与光感受器交换能量代谢物，以支持视网膜功能。葡萄糖和脂质代谢的代谢物相互关联，但RPE的专门脂质代谢和葡萄糖代谢是如何调节的尚不清楚。我们已经研究了这种独特的机制。方法：对不同条件下的人视网膜色素上皮细胞系ARPE-19进行比较筛选，以确定RPE代谢调节的相关因素。根据这些实验结果，我们选择了高迁移率基团核小体相关蛋白1 （HMGN1）作为候选，并分析了HMGN1缺失的ARPE-19 （HGMN1-/- ARPE-19）和HMGN1敲除小鼠（HMGN1 -/-小鼠）。结果：HMGN1通过表达改变参与了能量代谢。HMGN1-/- ARPE-19细胞更倾向于脂肪酸氧化而不是葡萄糖代谢作为能量来源。Hmgn1-/-小鼠的附睾脂肪质量和血清脂质重量低于标准饮食的对照组，并表现出糖耐量受损。小鼠也表现出视网膜功能障碍，与视网膜电图测量的老年对照视网膜相似。然而，富含棕榈酸盐的饮食以及rpe特异性HMGN1的重新表达减轻了视网膜功能障碍。随着年龄的增长，HMGN1在RPE/脉络膜中特异性下调，这让人想起RPE/脉络膜中与年龄相关的代谢变化。结论：HMGN1参与能量代谢，其表达改变可调节rpe特异性代谢表型。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Investigative ophthalmology & visual science 医学-眼科学

CiteScore

6.90

自引率

4.50%

发文量

339

审稿时长

1 months

期刊介绍： Investigative Ophthalmology & Visual Science (IOVS), published as ready online, is a peer-reviewed academic journal of the Association for Research in Vision and Ophthalmology (ARVO). IOVS features original research, mostly pertaining to clinical and laboratory ophthalmology and vision research in general.