Lak Shermin, Kanavi Mozhgan Rezaei, Bayat Kia, Ahmadieh Hamid, Soheili Zahra-Soheila, Suri Fatemeh
Department of Molecular Medicine, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Ocular Tissue Engineering Research Center, Research Institute for Ophthalmology and Vision Science, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Exp Eye Res. 2025 Sep;258:110517. doi: 10.1016/j.exer.2025.110517. Epub 2025 Jul 11.
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.
年龄相关性黄斑变性（AMD）是一种神经退行性视网膜疾病，通常在晚年出现，是导致中心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主要的剪接变体，它们通过外显子10的排除或包含而有所不同，从而导致3R和4R异构体的表达。在各种神经退行性疾病中都观察到了Tau表达和4R-3R异构体比例的变化；然而，AMD中Tau mRNA的表达仍未得到探索。本研究首次调查了干性AMD患者中MAPT转录变体的表达情况。人类供体眼来自伊朗眼库，分为三类：干性AMD（年龄≥50岁，n = 13）、老年正常组（年龄≥50岁，n = 13）和年轻正常组（年龄≤40岁，n = 10）。分离视网膜RNA，并使用特异性引物通过定量实时PCR（qRT-PCR）评估总Tau以及3R和4R转录变体。干性AMD样本显示出3R和4R异构体的混合，与两个对照组相比，总Tau水平没有显著差异。然而，与两个对照组相比，干性AMD样本中的4R/3R比值显著更高，而老年对照组和年轻对照组之间没有观察到显著差异。这些发现表明，4R/3R Tau比值的变化可能在干性AMD的进展中起作用，可能触发促进疾病进展的途径。有必要进行进一步的研究，以在疾病的各个阶段探索这些结果。
