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

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.