Differential expression profiles of MAPT (TAU) gene isoforms in dry age-related macular degeneration

IF 3 2区医学 Q1 OPHTHALMOLOGY

Experimental eye research Pub Date : 2025-07-11 DOI:10.1016/j.exer.2025.110517

Shermin Lak , Mozhgan Rezaei Kanavi , Kia Bayat , Hamid Ahmadieh , Zahra-Soheila Soheili , Fatemeh Suri

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引用次数: 0

Abstract

Age-related macular degeneration (AMD) is a neurodegenerative retinal disorder that typically emerges later in life and is the primary cause of central visual loss. The microtubule-associated protein Tau (MAPT) gene produces six significant splice variants in neural cells, which are differentiated by the exclusion or inclusion of exon 10, resulting in expression of 3R and 4R isoforms. Changes in Tau expression and the ratio of 4R–3R isoforms have been observed in various neurodegenerative diseases; however, the expression of Tau mRNA in AMD remains unexplored. This study represents the first investigation into the expression of MAPT transcript variants in patients with dry AMD.

Human donor eyes were sourced from the Iranian Eye Bank and divided into three categories: Dry-AMD (aged ≥50 years, n = 13), Elderly-Normal (aged ≥50 years, n = 13), and Young-Normal (aged ≤40 years, n = 10). Retinal RNA was isolated, and quantitative real-time PCR (qRT-PCR) was employed to evaluate total Tau, as well as the 3R, and 4R transcript variants using specific primers.

Dry-AMD samples showed a mixture of 3R and 4R isoforms, with no significant difference in total Tau levels when compared to both control groups. However, the 4R/3R ratio was significantly higher in Dry-AMD samples compared to both control groups, while no significant difference was observed between elderly and young controls.

These findings indicate that changes in the 4R/3R Tau ratio may play a role in the progression of Dry-AMD, potentially triggering pathways that promote disease advancement. Further research is necessary to explore these results across various stages of the disease.

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干性年龄相关性黄斑变性中MAPT （TAU）基因亚型的差异表达谱

年龄相关性黄斑变性（AMD）是一种神经退行性视网膜疾病，通常出现在晚年，是中枢性视力丧失的主要原因。微管相关蛋白Tau （MAPT）基因在神经细胞中产生六种重要的剪接变异体，这些变异体通过排除或包含外显子10而分化，导致3R和4R亚型的表达。在各种神经退行性疾病中观察到Tau表达和4R与3R亚型的比值的变化；然而，Tau mRNA在AMD中的表达尚不清楚。这项研究首次研究了干性AMD患者中MAPT转录变异体的表达。供体眼来源于伊朗眼库，分为干性amd（≥50岁，n=13）、中老年正常眼（≥50岁，n=13）、年轻正常眼（≤40岁，n=10）三类。分离视网膜RNA，采用定量实时荧光定量PCR （qRT-PCR）技术，利用特定引物对Tau蛋白总量以及3R和4R转录物变体进行评估。干性amd样品显示3R和4R亚型的混合物，与两个对照组相比，总Tau水平无显著差异。然而，Dry-AMD样本的4R/3R比值明显高于两个对照组，而在老年和年轻对照组之间没有显著差异。这些发现表明，4R/3R Tau比值的变化可能在干性amd的进展中发挥作用，可能触发促进疾病进展的途径。需要进一步的研究来探索这种疾病不同阶段的结果。

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

Experimental eye research 医学-眼科学

CiteScore

6.80

自引率

5.90%

发文量

323

审稿时长

66 days

期刊介绍： The primary goal of Experimental Eye Research is to publish original research papers on all aspects of experimental biology of the eye and ocular tissues that seek to define the mechanisms of normal function and/or disease. Studies of ocular tissues that encompass the disciplines of cell biology, developmental biology, genetics, molecular biology, physiology, biochemistry, biophysics, immunology or microbiology are most welcomed. Manuscripts that are purely clinical or in a surgical area of ophthalmology are not appropriate for submission to Experimental Eye Research and if received will be returned without review.